Nanomachine compositions and methods of use

ABSTRACT

The invention provides a basic genetic operating system for an autonomous prototrophic nanomachine having a nanomachine genome encoding a minimal gene set sufficient for viability. Also provided is a basic genetic operating system for an autonomous auxotrophic nanomachine having a nanomachine genome encoding a minimal gene set sufficient for viability in the presence of an auxotrophic biomolecule. The minimal gene set encoded by the basic genetic operating system can contain the functional categories of transcription, translation, aerobic metabolism, glycolysis/pyruvate dehydrogenase/pentose phosphate pathways, carbohydrate metabolism, central intermediary metabolism, nucleotide metabolism, transport and binding proteins, and housekeeping functions. Functional categories can be arranged in a predetermined physical or temporal order. A prototrophic basic genetic operating system sufficient for autonomous viability can contain a minimal gene set of about 152 or less fundamental genes, orthologs or nonothorologous displacements thereof. An auxotrophic basic genetic operating system sufficient for autonomous viability in the presence of an auxotrophic biomolecule can contain about 151 or less fundamental genes, orthologs or nonothorologous displacements thereof. Also provided is a basic genetic operating system sufficient for autonomous prototrophic or auxotrophic viability which can have an expression control region for the production of a biomolecule. Viable autonomous prototrophic and auxotrophic nanomachines are also provided.

BACKGROUND OF THE INVENTION

[0001] This application claims benefit of the filing date of U.S.Provisional Application No. 60/______, filed Sep. 20, 2001, which wasconverted from U.S. Ser. No. 09/960,607, and which is incorporatedherein by reference.

[0002] This invention relates generally to organismic biology and, morespecifically to construction and operation of DNA-based nanomachines.

[0003] The diagnosis and treatment of human diseases continues to be amajor area of social concern. The importance of improving health care isself-evident, so long as there continues to be diseases that affectindividuals, there will be an effort to understand the cause of suchdiseases as well as efforts to diagnose and treat such diseases.Preservation of life is an inherent force motivating the vast amount oftime and expenditure continually invested into scientific discovery anddevelopment processes. The application of results from these scientificprocess to the medical field has led to surprising advancements indiagnosis and treatment over the last century, and especially over thelast quarter century. Such advancements have improved both the qualityof life and life-span of affected individuals.

[0004] However significant in both scientific and medical contributionto their respective fields, the progression of advancements have beenslow and painstaking, generally resulting from step-wise trial and errorhypothesis-driven research. Moreover, with each advancement there can becumulative progression in the overall scientific understanding of aproblem but there is no guarantee that the threshold needed to translatea discovery into a practical medical application has been achieved.Additionally, with the achievement of all too many advancements comesthe sobering realization that the perceived final answer for a completeunderstanding of a particular physiological or biochemical process is,instead, just a beginning to a more complex process still needed to bedissected and understood.

[0005] Further complicating the progression of scientific advancementsand their practical application can result from technical limitations inavailable methodology or materials. Each discovery or advancement canpush the frontiers of science to new extremes. Many times, continuedprogress can be stalled due to the unavailability or insufficiency intechnological sophistication needed to continue studies at the newextremes. Therefore, further advancements in the scientific discoveryand medical fields necessarily have to await progress in other fieldsfor the advent and development of more capable technologies andmaterials. As a result, the progression of scientific advancementshaving practical diagnostic and therapeutic applications can occurrelatively slowly because it results from the accumulation of manysmaller discoveries, contributions and advancements in technologies.

[0006] Nanotechnology has been one such scientific advancement purportedto open new avenues into the discovery and development processes andachieve new dimensions in the medical diagnostic and therapeutic fields.Nanotechnology has been described as the production of systems on theorder of one to one hundred nanometers in size or the manipulation ofmatter at the atomic level. Futuristic speculation of nanotechnology formedical applications has been directed to the production of miniaturedevices and machines that in effect mimic or control biochemical processthrough hybrid biomechanical and bioelectrical assemblies. Similarly,the construction of nanostructures also has been purported as anadvancement that will revolutionize diagnostic applications because oftheir precise physical characteristics and comparable size to theirmolecular targets.

[0007] The construction of atomic level substances through molecularmanipulation is a technology imagined five decades ago. Similarly, theidea of merging biological and nonbiological materials also is not new.With the expanding availability of a variety of materials and withadvancements in physical and chemical methods for manipulation of matterat the nanoscale level, the construction of structures with highlycontrolled and unique properties can be accomplished. A fledglingindustry has now emerged which is attempting to exploit these propertiesof nanostructures. However, except for physical and chemical approachesfor manipulating matter, the application of nanotechnology to biology isstill in the conception stage.

[0008] Therefore, while spectacular in its potential ramifications,nanotechnology as initially imagined has not yet come to fruition.Despite the numerous descriptions of miniature devices and machinesprobing and surveying the body, the only commercial applications toresult from nanotechnology have been dirt-repelling surface coatings andpaint additives. One drawback hindering the application and developmentof nanotechnology to biology is due to its bottom-up synthesis approachfrom single atoms or molecules for precise miniaturization. Such anapproach requires sophisticated and advanced technology derived from thecombination of numerous disciplines. However, for many assembly steps,the envisioned technology required for precise synthesis of complicatednanodevices and biomechanical machines is not yet available or fullydeveloped.

[0009] Thus, there exists a need for nanoscale compositions with definedcharacteristics that can probe and mimic physiological and biochemicalprocesses without hindrance by limitations in technology development.The present invention satisfies this need and provides relatedadvantages as well.

SUMMARY OF THE INVENTION

[0010] The invention provides a basic genetic operating system for anautonomous prototrophic nanomachine having a nanomachine genome encodinga minimal gene set sufficient for viability. Also provided is a basicgenetic operating system for an autonomous auxotrophic nanomachinehaving a nanomachine genome encoding a minimal gene set sufficient forviability in the presence of an auxotrophic biomolecule. The minimalgene set encoded by the basic genetic operating system can contain thefunctional categories of transcription, translation, aerobic metabolism,glycolysis/pyruvate dehydrogenase/pentose phosphate pathways,carbohydrate metabolism, central intermediary metabolism, nucleotidemetabolism, transport and binding proteins, and housekeeping functions.Functional categories can be arranged in a predetermined physical ortemporal order. A prototrophic basic genetic operating system sufficientfor autonomous viability can contain a minimal gene set of about 152 orless fundamental genes, orthologs or nonothorologous displacementsthereof. An auxotrophic basic genetic operating system sufficient forautonomous viability in the presence of an auxotrophic biomolecule cancontain about 151 or less fundamental genes, orthologs ornonothorologous displacements thereof. Also provided is a basic geneticoperating system sufficient for autonomous prototrophic or auxotrophicviability which can have an expression control region for the productionof a biomolecule. Viable autonomous prototrophic and auxotrophicnanomachines are also provided.

[0011] Further provided is a basic genetic operating system for anautonomous prototrophic nanomachine having a nanomachine genome encodinga minimal gene set sufficient for autonomous prototrophic replication.Also provided is a basic genetic operating system for an autonomousauxotrophic nanomachine having a nanomachine genome encoding a minimalgene set sufficient for autonomous replication in the presence of anauxotrophic biological molecule. The minimal gene set encoded by thebasic genetic operating system can direct synthesis of the minimal geneset in a relative order of functional categories corresponding toreplication, transcription, translation, aerobic metabolism andglycolysis/pyruvate dehydrogenase/pentose phosphate pathways. Additionalfunctional categories can be for carbohydrate metabolism, centralintermediary metabolism, nucleotide metabolism, signal transductionregulation, transport and binding proteins, particle division, chaperonesystem, fatty acid/lipid metabolism, particle envelope and housekeepingfunctions. The functional categories can be arranged in a predeterminedphysical or temporal order. A prototrophic basic genetic operatingsystem sufficient for autonomous replication can contain about 247 orless fundamental genes, orthologs or nonorthologous displacementsthereof. An auxotrophic basic genetic operating system sufficient forautonomous replication in the presence of an auxotrophic biomolecule cancontain about 246 or less fundamental genes, orthologs ornonothorologous displacements thereof. Also provided is a basic geneticoperating system sufficient for autonomous prototrophic or auxotrophicreplication which can have an expression control region for theproduction of a biomolecule. Replication competent autonomousprototrophic and auxotrophic nanomachines are also provided.

BRIEF DESCRIPTION OF THE DRAWINGS

[0012]FIG. 1 shows fundamental genes and functional categories of abasic genetic operating system for a viable prototrophic nanomachine.

[0013]FIG. 2 shows fundamental genes and functional categories of abasic genetic operating system for a replication competent prototrophicnanomachine.

DETAILED DESCRIPTION OF THE INVENTION

[0014] This invention is directed to biological nanomachines programedand self-produced by nucleic acid-based information. Nanomachine genomescan be created that encode all essential information for autonomousexistence and operation. Additionally, nanomachines can be programmed toperform essentially any activity exhibited by cellular life. Nanomachineprogramming is implemented through nucleic acid-based information.Genetic instructions can be created, such as a genetic operating system,that encodes all functions sufficient for a biological nanomachine ofthe invention to self-produce required components and perform cellularlife functions. The biological nanomachines of the invention can befurther programmed to perform a wide variety of activities bymodification of their genome to incorporate or modify a predeterminedfunction. Therefore, additional genes can be added to the geneticoperating system which encode further instructions sufficient toself-produce and maintain supplemental cellular functions andactivities. Versatility is one advantage of the nanomachines of theinvention because they can be programmed for minimal functions, basiccellular life functions or to additionally include a wide variety ofcomplicated activities.

[0015] The genetic instructions, or nucleic acid material, are readusing ordinary cellular machinery and converted into other nucleicacids, polypeptides, macromolecules or other organic compounds thatperform the work of the encoded cellular functions. The nanomachines ofthe invention are therefore produced through biosynthesis of constituentcomponents and self-assembly into functional biological structures.Using nucleic acid-based information, biochemical rules and complexmechanisms of manipulating matter can be reliably harnessed without theneed for sophisticated or advanced nanotechnology. Therefore, anotheradvantage of the biological nanomachines of the invention is that theycan be produced and maintained by bottom-up synthesis using rules andself-assembly processes of nature that have been evolutionary selectedand are well understood. Moreover, the use of nucleic acid encodedinformation is a further advantage of the invention because it can bemaintained through biological replication processes and can becontinually employed to direct the production of constituent nanomachinecomponents through reliable biosynthetic processes.

[0016] In one embodiment, the invention is directed to a basic geneticoperating system that is sufficient to sustain viability for anautonomous nanomachine. A basic genetic operating system is ananomachine genome which contains the genetic programming required todirect the synthesis and operation of an autonomous nanomachine. Suchgenetic programming consists of a minimal gene set sufficient to carryout component synthesis required for fundamental functions of anautonomous nanomachine. A minimal compilation of genes with sufficientinformation to support viability will contain, for example, genesrequired to effect basic cellular and biochemical process such astranscription, translation and energy production as well as other basiccellular homeostasis processes such as nucleotide metabolism,carbohydrate metabolism, central intermediate metabolism andhousekeeping functions. In a specific embodiment, such a basic geneticoperating system specifying nanomachine viability contains about 152genes. Additional genes or gene sets, such as for the production of atherapeutic polypeptide or diagnostic indicator, can be incorporatedinto the basic genetic operating system to generate a genome furtherprogrammed to execute and carry out activities and operations additionalto those specified by the basic operating system. The basic geneticoperating systems of the invention also can be harbored in a lipidvesical or other biologically compatible materials to produce anautonomous nanomachine of the invention.

[0017] In another embodiment, the invention is directed to a basicgenetic operating system for autonomous nanomachines that arereplication competent. A minimal gene set sufficient to carry outcomponent synthesis for fundamental functions of replication competentnanomachines can contain in addition to those required for viability,genes required for replication, particle division, fatty acid/lipidmetabolism and particle envelope components, for example. In a specificembodiment, such a basic genetic operating system specifying areplication competent nanomachine contains about 247 genes. Additionalgenetic programming can be overlaid onto a basic genetic operatingsystem directing autonomous replication by incorporating instructionsfor a wide variety of activities and operations into the nanomachinegenome. Therefore, replication competent nanomachines can beadvantageously used for persistent performance of useful activities suchas the production of therapeutic polypeptides or diagnostic indicators.Basic genetic operating systems specifying replication competence can beharbored in lipid bilayer membranes directed and synthesized from thenanomachine's basic genetic operating system as well as a lipid vesicalor other biologically compatible material to produce an replicationcompetent autonomous nanomachine of the invention.

[0018] In another embodiment, autonomous nanomachines of the inventioncan be programmed with prototrophic or auxotrophic basic geneticoperating systems. A nanomachine harboring a prototrophic basic geneticoperating system is a genotypically complete genome so as to encode allmandatory gene products for nanomachine autonomy. For example, aprototrophic nanomachine programmed with a basic genetic operatingsystem conferring replication competence will encode the requisite geneproducts sufficient to sustain replication similar to cellular lifeforms. A nanomachine harboring an auxotrophic basic genetic operatingsystem is an incomplete genome for at least one gene product requiredfor nanomachine autonomy. Autonomy can be conferred on such auxotrophicnanomachines programmed with a basic genetic operating system byexogenously suppling the gene product or biosynthetic intermediate tothe nanomachine.

[0019] As used herein, the term “basic” when used in reference to agenetic operating system, is intended to mean a elementary orfoundational set of genetic instructions that can direct an autonomousfunction of a nanomachine. An elementary or foundational set of geneticinstructions will contain, for example, a substantially non-redundantset of genes that encode a minimal number of gene products required toeffect one or more autonomous functions of a nanomachine. Substantiallynon-redundant genetic instructions are genes or gene sets that arenon-coextensive in structure or function and include similar butfunctionally distinguishable genes or gene sets and their respectivegene products. The term basic therefore refers to an underlying set ofgenes that encode products required for fundamental activities of ananomachine. A basic genetic system therefore provides the essentialgenetic program which directs autonomy of a nanomachine. A basic systemalso allows for the integration of additional genetic programs that,when executed, can perform a variety of other activities, including forexample, preforming useful work or directing the production of usefulmolecules and biological processes.

[0020] As used herein, the term “genetic operating system” is intendedto mean a genetic program or set of instructions encoded in a nucleicacid that controls the operation of one or more autonomous functions ofa nanomachine. A genetic operating system therefore specifiesnanomachine gene products that provide fundamental activities and directthe regulation of such activities to achieve functional autonomy. Agenetic operating system also controls integration and directs theregulation and execution of additional genetic programs that can performnumerous general or specialized functions of a nanomachine. Suchoverlying or operating system-dependent genetic programs specify, forexample, non-autonomous functions of a nanomachine as they are dependenton the underlying basic genetic operating system to supply components oractivities essential for initiation, execution or completion of theencoded task. A genetic operating system can encode genes sufficient forthe control and operation of a single autonomous nanomachine function aswell as for the control, integration and operation of multipleautonomous functions, including for example, nanomachine viability,replication and proliferation.

[0021] The structure of a genetic operating system can be arranged in avariety of different formats so long as it encodes sufficient geneticinformation for the control and operation of one or more autonomousfunctions of a nanomachine. For example, a genetic operating system canbe composed of a single nucleic acid genome containing a completeintegrated set of genes that specify the functionality of the basicoperating system. Alternatively, it can be composed of two or morenucleic acid genomes that together specify the functionality of thebasic operating system. Similarly, genes which make up a geneticoperating system can be integrated into a nanomachine genome in anyarrangement so long as they direct the control and operation of anencoded autonomous function. For example, constituent genes can beorganized linearly, functionally or randomly within the geneticoperating system. Similarly, constituent genes can be composed ofsubsets, defined for example, by various structural or functionalcriteria known to those skilled in the art, and such subsets or modulescan be organized linearly, functionally or randomly within the geneticoperating system. Therefore, so long as the genetic operating systemsufficiently encodes and produces gene products that execute the controland operation of an autonomous nanomachine function, the structure of agenetic operating system can be arranged, for example, as a single ormultiple component genome, with fundamental genes individually ormodularly integrated, or in a linear, functional or random organization.

[0022] As used herein, the term “autonomous” is intended to meanindependent operation. Independence is used to characterize anautonomous operation in relation to an engineered activity of areferenced nanomachine or process thereof. Therefore, an autonomousoperation or activity can function on its own resources given aparticular environment consistent with the engineered activity orfunction. Similarly, an autonomous operation or activity can beperformed without the need for external sources of nucleicacid-encodable molecules for production, activity, regulation orhomeostasis, for example, with respect to the referenced nanomachineoperation or activity. Autonomous operations or activities of ananomachine include, for example, viability, replication, proliferationor protein synthesis. The term “autonomous” is intended to include, forexample, dependence on external sources of essential nutritionalrequirements for survival. Such essential nutritional requirementsinclude, for example, a carbon source, an oxygen source for aerobicconditions, a nitrogen source, and inorganic compounds. Autonomousoperation also can include, for example, dependence on a sulphur source.

[0023] For example, a protrotrophic nanomachine capable of autonomousreplication harbors sufficient nucleic acid-encodable information tosynthesize the required molecules necessary to generate and performobligatory processes for replication. Therefore, a autonomousprototrophic nanomachine that is replication competent can carry outtranscription, translation and nucleic acid replication functionswithout dependence on external sources for encodable factors such asmacromolecules. Self-contained replication would be one phenotype ofsuch a replication competent prototrophic nanomachine. The genotype ofsuch a prototrophic nanomachine will consist of requisite genesnecessary to initiate and execute the biological functions oftranscription, translation, replication and energy production.

[0024] Similarly, an auxotrophic nanomachine capable of autonomousreplication will harbor sufficient nucleic acid-encodable information tosynthesize the required molecules necessary to generate and performobligatory processes for replication with the inclusion of one or moreauxotrophic biological molecules. Therefore, a autonomous auxotrophicnanomachine that is replication competent can carry out transcription,translation and nucleic acid replication functions without dependence onexternal sources for encodable factors other than an auxotrophicmolecule. Self-contained replication in the presence of an auxotrophicmolecule would be one phenotype of such a replication competentauxotrophic nanomachine. The genotype of such a auxotrophic nanomachinewill consist at least one defective gene corresponding to an auxotrophicmolecule as well as all other requisite genes necessary to initiate andexecute the biological functions of transcription, translation,replication and energy production.

[0025] As used herein, the term “prototroph” or “prototrophic” isintended to mean a nanomachine, or operation thereof, having thenutritional requirements corresponding to a referenced phenotype of agenotypically complete nanomachine. A nanomachine, or operation thereof,is genetypically complete when it encodes the requisite obligatory geneproducts to synthesize required biological components and autonomouslyperform the engineered activity or activities in the referencedphenotype. A referenced phenotype of a nanomachine, or operationthereof, is also referred to as a wild type phenotype when used todescribe an operation or activity of a genotypically completenanomachine. Therefore, a prototrophic nanomachine references thedesigned nutritional requirements corresponding to the engineeredactivity or activities of a genotypically complete nanomachine.

[0026] For example, where an engineered activity is amino acid synthesisthrough salvage pathways, obligatory encoded gene products of agenotypically complete nanomachine would consist of the required salvagepathway enzymes for amino acid synthesis. Similarly, where de novo aminoacid synthesis is an engineered activity, a genotypically completenanomachine would consist of the required set of encoded gene productssufficient to biochemically synthesize all twenty naturally occurringamino acids. In both of the above specific examples, the referencephenotype can be replication competent. The former having an engineeredactivity of salvage synthesis of amino acids whereas the latter havingan engineered activity of de novo amino acid synthesis.

[0027] As used herein, the term “auxotroph” or “auxotrophic” is intendedto mean a nanomachine, or operation thereof, having the nutritionalrequirements corresponding to a referenced phenotype of a genotypicallyincomplete nanomachine. A nanomachine, or operation thereof, isgenetypically incomplete when it is deficient in encoding at least oneobligatory gene product for synthesis of required biological componentssufficient for autonomous performance of the engineered activity oractivities of the referenced phenotype. Therefore, an auxotrophicnanomachine references the requirement of the deficient gene product, ora downstream product, that can restore autonomous performance of theengineered activity or activities in addition to referencing thedesigned nutritional requirements corresponding to the engineeredactivity of an otherwise genotypically complete nanomachine.

[0028] For example, where an engineered activity is nucleotide synthesisthrough salvage pathways and the nanomachine is auxotrophic for purines,nutritional requirements would include a supply of purines or precursorsof purines. The obligatory encoded gene products of an otherwisegenotypically complete nanomachine would consist of the required salvagepathway enzymes for complete nucleotide synthesis except for one or moregene products in the purine salvage pathway. Similarly, where de novonucleotide synthesis is an engineered activity, nutritional requirementswould include a supply of substrates or precursors, or a downstreamproduct within the pathway. An otherwise genotypically completenanomachine would consist of the required set of encoded gene productssufficient to biochemically synthesize all naturally occurringnucleotides. In both of the above specific examples, the referencephenotype can be replication competent. The former having an engineeredactivity of salvage synthesis of nucleotides whereas the latter havingan engineered activity of de novo nucleotide synthesis.

[0029] An “auxotrophic biological molecule” or “auxotrophic biomolecule”as it is used herein, is a molecule that restores autonomy to anauxotrophic nanomachine, or operation thereof, when supplied in thegrowth medium or living environment of the nanomachine. Similarly, thegene or genes responsible-for the referenced biosynthetic defect isreferred to herein as an “auxotrophic gene” or “auxotrophic genes.”

[0030] As used here, the term “nanomachine” is intended to mean abiochemically-based particle that can be genetically programed toperform biochemical or physiological work. Biochemically-based particlesare those bodies that can synthesize components required for autonomousfunction from molecules found in nature, including for example, thosemolecules in physiological systems. Therefore, a biochemically-basedparticle also can be considered a nucleic acid-based particle where theinstructions required for component synthesis are encoded in a nucleicacid. Generally, a nanomachine will contain at least a basic geneticoperation system and a particle envelope. A particle envelope can be,for example, a physical partition or other physical or chemical meanswhich can control a microenvironment. The basic genetic operating systemdirects, for example, the control and operation of autonomousnanomachine functions whereas the particle envelope partitions, forexample, nanomachine components from non-nanomachine components. Ananomachine also can contain, for example, additional genetic programsthat perform numerous general or specialized biochemical activities of ananomachine. Biochemical or physiological work of a nanomachine caninclude, for example, particle viability, proliferation, replication,transcription and translation. Moreover, a nanomachine can be loadedwith various additional components either pre- or post-operationalstart-up and still be included within the meaning of the term. Theactual shape or size of a nanomachine can vary so long as it is abiochemically-based particle and is, or can be made to be, geneticallyprogramed to perform biochemical or physiological work.

[0031] As used herein, the term “minimal” when used in reference to agene set is intended to mean a substantially non-redundant thresholdnumber of genes that are sufficient or adequate to perform a referencedactivity. Therefore, a minimal set of genes are those genes that arerequired to competently perform a referenced nanomachine activity. Forexample, a minimal gene set can be specific to a referenced functionalcategory such as replication or aerobic metabolism. Alternatively, aminimal gene set can be directed to combined functions of a referencedactivity such as replication competency or viability. A threshold numberof genes can be, for example, at least those genes that areindispensable to the performance of a nanomachine operation or activityencoded by the referenced gene set. A threshold number of genes also caninclude, for example, other genes able to increase the competency of theprocess without substantial overlap in gene product function. Therefore,a minimal gene set can be, or will include for example, the leastpossible number of genes sufficient to perform a referenced operation oractivity.

[0032] It is understood that a minimal gene set is not restricted togenes derived from one species or even from a few different species.Instead, minimal gene sets can be composed of all genes derived from thesame species, different related species, different divergent species orfrom various combinations thereof. Such species can include, forexample, procaryotes such as Mycoplasma genitalium, Haemophilusinfluenzae and Escherichia coli, and eucaryotes such as yeast,nematodes, insects, other invertebrates, vertebrates, mammalian,including rodent, primate and human. Minimal gene sets include, forexample, those for M. genitalium, H. influenzae, and E. coli describedby Fraser et al., Science, 270:397-403 (1995); Mushegian and Koonin,Proc. Natl. Acad. Sci. U.S.A., 93:10268-73 (1996); Koonin et al., TrendsGenet., 12, 334-336 (1996); Hutchison et al., Science, 286:2165-69(1999), or at NCBI URL ncbi.nlm.nih.gov/cgi-bin/Complete_Genomes/mglist,all of which are incorporated herein by reference. A set of fundamentalgenes is a further specific example of a minimal gene set.

[0033] As used herein, the term “fundamental” when used in reference toa gene is intended to mean a gene that is important or essential toperformance of a referenced activity. Therefore, a fundamental gene orset of genes are those genes that without which the congnate gene set orgenetic operating system as a whole would inadequately perform areferenced nanomachine activity. A fundamental gene can include, forexample, a gene that is indispensable to the performance of ananomachine operation or activity encoded by the referenced gene set. Aset of fundamental genes will include, for example, a substantiallynon-redundant threshold number of genes that are important or sufficientto perform a referenced nanomachine activity. Therefore, a set offundamental genes will be composed of the least possible number of genessufficient to perform a referenced operation or activity. Specificexamples of fundamental gene sets for a viable nanomachine and for areplication competent nanomachine are show in FIGS. 1 and 2,respectively.

[0034] As with minimal gene sets, it is understood that fundamentalgenes of the nanomachine genomes and genetic operating systems of theinvention are not restricted to genes derived from one species or evenfrom a few different species. Instead, fundamental genes can be obtainedfrom the same species, different related species, different divergentspecies or from various combinations thereof. Similarly, such speciescan include, for example, procaryotes such as Mycoplasma genitalium,Haemophilus influenzae and Escherichia coli, and eucaryotes such asyeast, nematodes, insects, other invertebrates, vertebrates, mammalian,including rodents, primates, and human.

[0035] It is also understood that fundamental genes within a minimalgene set derived from the same or different species can be modified torepresent a different codon usage or preference. For example, the codingregion for M. genitalium genes can be altered to encode E. coli type I,II or III codon preferences. Such modifications can be useful where thebasic genetic operating system will function in, for example, an E. colibiosynthetic environment. Additionally, altering codon preferences alsocan be useful when, for example, fundamental genes originate from two ormore different species. In such an example, orthologs or nonorthologousgene displacements from one species can be engineered to encode the sameor substantially the same polypeptide from a heterologous codonpreference. Therefore, all fundamental genes within a basic geneticoperating system or genome can be normalized to a predetermined codonusage. Additionally, further modifications can be made in the codonusage to adjust for wobble and therefore frequency of amino acidincorporation. Other modifications to the encoding nucleic acid sequencewell known to those skilled in the art which do not substantially affectthe function of the gene or its gene product also can be introduced. Itis also understood that various modifications described herein inreference to fundamental genes also are applicable to non-fundamentalgenes included in a nanomachine genome.

[0036] As used herein, the term “ortholog” is intended to mean a gene orgenes that are related by vertical descent and are responsible forsubstantially the same or identical functions in different organisms.For example, mouse epoxide hydrolase and human epoxide hydrolase can beconsidered orthologs for the biological function of hydrolysis ofepoxides. Genes are related by vertical descent when, for example, theyshare sequence similarity of sufficient amount to indicate they arehomologous, or related by evolution from a common ancestor. Genes canalso be considered orthologs if they share three-dimensional structurebut not necessarily sequence similarity, of a sufficient amount toindicate that they have evolved from a common ancestor to the extentthat the primary sequence similarity is not identifiable. Genes that areorthologous can encode proteins with sequence similarity of about 25% to100% amino acid sequence identity. Genes encoding proteins sharing anamino acid similarity less that 25% can also be considered to havearisen by vertical descent if their three-dimensional structure alsoshows similarities. Members of the serine protease family of enzymes,including tissue plasminogen activator and elastase, are considered tohave arisen by vertical descent from a common ancestor.

[0037] It is understood that the term is intended to include genes ortheir encoded gene products that through, for example, evolution havediverged in structure or overall activity. For example, where onespecies encodes a gene product exhibiting two functions and where suchfunctions have been separated into distinct genes in a second species,the three genes and their corresponding products are considered to beorthologs. An example of orthologs exhibiting separable activities iswhere distinct activities have been separated into distinct geneproducts between 2 or more species or within a single species. Aspecific example is the separation of elastase proteolysis andplasminogen proteolysis, two types of serine protease activity, intodistinct molecules as plasminogen activator and elastase. A secondexample is the separation of mycoplasma 5′-3′ exonuclease and DrosophilaDNA polymerase III activity. The DNA polymerase from the first speciescan be considered an ortholog to either or both of the exonuclease orthe polymerase from the second species and vice versa.

[0038] It is also understood that orthologs can be created artificiallyby, for example, combining domains or portions of polypeptides fromdifferent species to create entirely new polypeptides with uniquefunctions or combinations of functions. Such domains, eitherindividually or when combined into unique polypeptides, can beconsidered orthologous to genes or gene domains related by verticaldescent and responsible for substantially the same function in differentorganisms. Similarly, a unique combination of domains or portions alsocan be considered an ortholog to a second unique combination generatedfrom different but orthologous domains. Functions of orthologs ororthologous domains include, for example, enzymatic, catalytic, signaltransduction, structural and mechanical as well as other activities wellknown to those skilled in the art.

[0039] In contrast, paralogs are homologs related by, for example,duplication followed by evolutionary divergence and have similar orcommon, but not identical functions. Paralogs can originate or derivefrom, for example, the same species or from a different species. Forexample, microsomal epoxide hydrolase (epoxide hydrolase I) and solubleepoxide hydrolase (epoxide hydrolase II) can be considered paralogsbecause they represent two distinctienzymes, co-evolved from a commonancestor, that catalyze distinct reactions and have distinct functionsin the same species. Other examples of paralogs include members of thehemoglobin (globin) family, members of the serine protease family, andimmunoglobulin heavy chain gene products. Paralogs are proteins from thesame species with significant sequence similarity to each othersuggesting that they are homologous, or related through co-evolutionfrom a common ancestor. Groups of paralogous protein families includeHipA homologs, luciferase genes, peptidases, and others. Moreover, aswith orthologs and orthologous domains, paralogs and paralogous domainssimilarly can be separated into distinct genes and gene products by, forexample, evolutionary divergence or by genetic or recombinantmanipulation.

[0040] As used herein, the term “nonorthologous gene displacement” isintended to mean a nonorthologous gene from one species that cansubstitute for a referenced gene function in a different species.Substitution includes, for example, being able to perform substantiallythe same or a similar function in the species of origin compared to thereferenced function in the different species. Although generally, anonorthologous gene displacement will be identifiable as structurallyrelated to a known gene encoding the referenced function, lessstructurally related but functionally similar genes and theircorresponding gene products nevertheless will still fall within themeaning of the term as it is used herein. Functional similarityrequires, for example, at least some structural similarity in the activesite or binding region of a nonorthologous gene compared to a geneencoding the function sought to be substituted. Therefore, anonorthologous gene includes, for example, a paralog or an unrelatedgene.

[0041] The M. genitalium gene MG262 is one specific example of anonorthologous gene displacement for the RNase H encoded function in H.influenzae and other species because it exhibits sequence identity toDNA polymerase 5′-3′ exonuclease and is distantly related to RNase H.Other specific examples of nonorthologous gene displacements include theM. genitalium genes MG264 and MG268 for the nucleoside diphosphatekinase (Ndk) encoded function in, for example, H. influenzae and E.coli. As with orthologs and paralogs, gene products of nonorthologousgene displacements are intended to be included within the meaning of theterm as it is used herein.

[0042] Orthologs, paralogs and nonorthologous gene displacements can bedetermined by methods well known to those skilled in the art. Forexample, inspection of nucleic acid or amino acid sequences for twopolypeptides will reveal sequence identity and similarities between thecompared sequences. Based on such similarities, one skilled in the artcan determine if the similarity is sufficiently high to indicate theproteins are related through evolution from a common ancestor.Algorithms well known to those skilled in the art, such as Align, BLAST,Clustal V and others compared and determine a raw sequence similarity oridentity, and also determine the presence or significance of gaps in thesequence which can be assigned a weight or score. Such algorithms alsoare known in the art and are similarly applicable for determiningnucleotide sequence similarity or identity. Parameters for sufficientsimilarly to determine relatedness are computed based on well knownmethods for calculating statistical similarity, or the chance of findinga similar match in a random polypeptide, and the significance of thematch determined. A computer comparison of two or more sequences can, ifdesired, also be optimized visually by those skilled in the art. Relatedgene products or proteins can be expected to have a high similarity, forexample, 25% to 100% sequence identity. Proteins that are unrelated canhave an identity which is essentially the same as would be expected tooccur by chance, if a database of sufficient size is scanned (about 5%).Sequences between 5% and 24% may or may not represent sufficienthomology to conclude that the compared sequences are related. Additionalstatistical analysis to determine the significance of such matches giventhe size of the data set can be carried out to determine the relevanceof these sequences.

[0043] Exemplary parameters for determining relatedness of two or moresequences using the BLAST algorithm, for example, can be as set forthbelow. Briefly, amino acid sequence alignments can be performed usingBLASTP version 2.0.8 (Jan. 5, 1999) and the following parameters:Matrix: 0 BLOSUM62; gap open: 11; gap extension: 1; x_dropoff: 50;expect: 10.0; wordsize: 3; filter: on. Nucleic acid sequence alignmentscan be performed using BLASTN version 2.0.6, (Sep. 16, 1998) and thefollowing parameters: Match: 1; mismatch: -2; gap open: 5; gapextension: 2; x_dropoff: 50; expect: 10.0; wordsize: 11; filter: off.Those skilled in the art will know what modifications can be made to theabove parameters to either increase or decrease the stringency of thecomparison, for example, and determine the relatedness of two or moresequences.

[0044] As used herein, the term “functional category” is intended tomean an operational classification of genes based on their purpose incellular life. The term is therefore intended to group genes and theirrespective gene products according to functional contribution to areferenced biochemical process or activity. For example, genes thatparticipate in replication processes will be classified as genes in thereplication functional category. DNA polymerase is one specific exampleof a replication gene. Similarly, RNA polymerase is a specific exampleof a gene classified in the transcription functional category. Anexemplary listing of functional categories and fundamental genescontained in each category is show in FIGS. 1 and 2 for basic geneticoperating systems for a viable nanomachine and for a replicationcompetent nanomachine, respectively. Although some genes can participatein more than one functional category, it is understood that aclassification into a single category is a matter of convenience orsimplicity for ease of description, and not a hierarchical distinctionof importance in one category over another.

[0045] As used herein, the term “viable” or “viability” is intended tomean a that a host nanomachine is able to survive or exist in anenvironmental setting consistent with its engineered programming.Similarly, a basic genetic operating system containing a minimal geneset encoding gene products sufficient for viability also is intended tomean that the genetic programming encodes the requisite fundamentalgenes that enable a host nanomachine to survive or exist in anenvironmental setting compatible with the engineered genotype of thebasic genetic operating system. Environmental settings can include, forexample, natural, biochemical, physiological or industrial environmentsas well as in vivo, in situ or in vitro settings. Survival or existencecan be, for example, passive, such as where biochemical process orselective reactions thereof are suspended until a favorable change inenvironmental conditions occurs. Survival or existence also can be, forexample, active, such as where biochemical processes or selectivereactions thereof continue to be at least partially active. Duration ofsurvival can be from short, to long, to prolonged periods of time andinclude, for example, ranges of time from seconds and minutes to hours,days, weeks, months and years. The actual survival duration of aparticular host nanomachine will depend, for example, on the engineeredprogramming of the basic genetic operating system and the targeted hostnanomachine application.

[0046] As used herein, the term “replication” or “replication competent”is intended to mean that a host nanomachine is able to create at leastone duplicate copy of its genome in an environmental setting consistentwith its engineered programming. Similarly, a basic genetic operatingsystem containing a minimal gene set encoding gene products sufficientfor replication also is intended to mean that the genetic programmingencodes the requisite fundamental genes that enable a host nanomachineto duplicate at least one copy of its genome in an environmental settingcompatible with the engineered genotype of the basic genetic operatingsystem. Therefore, the term replication refers to biosynthesis of a hostnanomachine's basic genetic operating system and, for example, othergenes encoded in its genome. Genome replication can include, forexample, regulated, conditional or constitutive modes of genomebiosynthesis. In contrast, proliferation, reproduction or particledivision can refer to duplication of a nanomachine particle envelope toproduce two or more progeny nanomachines. In the absence of particledivision, a replication competent nanomachine can accumulate, forexample, 2, 3, 4, 5, 10, 20 or 50 or more nanomachine genome copieswithin a particle envelope. Inclusion of particle division fundamentalgenes within a replication competent basic genetic operating system canallow, for example, concomitant segregation of single or multiple copiesof a nanomachine genome into progeny nanomachine particles.

[0047] As used herein, the term “devoid” when used in reference to agene is intended to mean lacking or deficient for a functional gene.Functional gene as it is referred to herein means that it encodes for aactive gene product, including for example, both nucleic acid andpolypeptide gene products. A functional gene can be lacking or deficientby, for example, deletion or mutation of its coding region, one or moreregulatory regions, or processing signals. Similarly, combinations ofalterations in coding regions, regulatory regions or processing signalsalso can render a gene set, basic genetic operating system ornanomachine genome devoid of a gene. Therefore, alterations in a genethat render it deficient for a functional gene product can be small,such as by a single point mutation, or large, such as by largedeletions, including all or substantially all of the encoding orregulatory region of the nucleic acid.

[0048] As used herein, the term “particle envelope” is intended to meana partition that separates or compartmentalizes nanomachine componentsfrom non-nanomachine components. The term additionally includes otherphysical or chemical means which can control compartmentalization into amicroenvironment. Such physical and chemical means include for example,electrostatic forces, hydrophobicity and micro encapsulation withoutcomplete partitioning. Nanomachine components include for example, ananomachine genome, including a basic genetic operating system, encodednucleic acid and polypeptide gene products and products producedtherefrom. Products produced from encoded gene products include, forexample, the multitude of metabolitic and catabolitic substrates,intermediates and products that can be synthesized by cellularbiochemical pathways. Such molecules include, for example, amino acids,nucleotides, nucleosides, purine and pyrimidine bases, fatty acids,lipids, carbohydrates, cofactors and other organic molecules. Anexemplary description of cellular biochemical pathways, includingsubstrates, intermediates and products, that are synthesized by nucleicacid encoded gene products can be found, for example, in LehninqerPrinciples of Biochemistry, Nelson and Cox, Third Edition, 2000, WorthPublishers, New York and Biochemistry, Stryer, Fourth Edition, 1995, W.H. Freeman and Company, New York, both of which are incorporated hereinby reference. In contrast, non-nanomachine components include, forexample, environmental components. A particle envelope can be composedof various biochemical molecules and physiologically-compatiblemolecules known to those skilled in the art.

[0049] For example, a particle envelop can be composed of substantiallythe same molecules as naturally occurring lipid membranes.Alternatively, a particle envelope can be completely or partiallysynthetic so long as it maintains its ability to partition nanomachinefrom non-nanomachine components. Particle envelopes also can be formedby, for example, surface tension, where nanomachine components are heldtogether in a droplet formed by surface tension or where aqueous mediapartitions separately in an organic solution. Separation to achieve aparticle envelope also can be spatially, such as between organic andnonorganic solutions or between an aqueous solution and air. Similarly,micro-porous structures also can be used to form a particle envelope.Specific examples can include porous resin and a micromachined matrix.Additionally, all of the various types of particle envelopes describedabove, as well as other types well known to those skilled in the art,also can be modified with charged moieties to either enable orsupplement separation of nanomachine components from non-nanomachinecomponents by electrostatic forces. Similarly, pressure and vacuumforces also can be used to create or enhance the function of a particleenvelope.

[0050] The invention is directed to biological nanomachines programmedby and synthesized from nucleic acid-based information. The use ofnucleic acid-based information enables the accurate assembly of matterat the atomic and molecular level into precise functional structures andoperational particle assemblages. Nucleic acid-based information allowsbottom-up assembly of nanoscale machines and structures because therules and processes for matter manipulation are inherently contained inthe encoding nucleic acid and conferred on the gene products as well.Therefore, Nucleic acid-based nanomachines programmed with geneticoperating systems circumvent top-down miniaturization approaches andrequirements for multi-disciplinary nanotechnology. Instead,nanomachines programmed by Nucleic acid-based information harnessbiochemical rules and processes to generate constituent nanomachinecomponents that self-assemble into functional biological andbiologically compatible structures which can perform useful work andcarry out a wide range of physiological and biochemical activities.

[0051] The invention provides a basic genetic operating system for anautonomous prototrophic nanomachine. The basic genetic operating systemconsists of a nanomachine genome encoding a minimal gene set sufficientfor viability. Functional categories of genes within a minimal gene setcan be transcription, translation, aerobic metabolism,glycolysis/pyruvate dehydrogenase/pentose phosphate pathways,carbohydrate metabolism, central intermediary metabolism, nucleotidemetabolism, transport and binding proteins, and housekeeping functions.

[0052] A basic genetic operating system of the invention is a nucleicacid, or a functional equivalent of a nucleic acid, that can serve as agenome for a biosynthetic cell or nanomachine. Functional equivalents ofa nucleic acid include, for example, a nucleic acid that contains one ormore natural or non-naturally occurring nucleotides, which containmodified bases or bases other than adenosine (A), guanine (G), cytosine(C) or thymine (T) or uracil (U) and which is a substrate fortemplate-directed nucleic acid polymerization. Modifications include,for example, derivatization and covalent attachment with chemicalgroups. Other bases can include, for example, pyrimidine or purineanalogs, precursors such as inosine that are capable of base pairformation, and tautomers. Similarly, a nucleic acid functionalequivalent also can contain modified or derivative forms of the riboseor deoxyribose sugar moieties, including, for example, functionalanalogs thereof. Those skilled in the art will know what natural ornon-naturally occurring nucleotide, nucleoside or base forms can be usedin a basic genetic operating system of the invention, includingderivatives and analogs thereof, and also capable of supportingtemplate-directed nucleic acid polymerization.

[0053] A basic genetic operating system encodes, for example, therequired gene products that are obligatory to sustain rudimentary orfoundational functions of cellular life. A basic genetic operatingsystem differs from a complete genome, for example, because itduplicates or more closely approximates a genetic copy of genes, orfunctional fragments thereof, that are essential for basic cellular lifefunctions. Therefore, a basic genetic operating system is a streamlinedgenome that contains all necessary genetic information required tosustain viability or other cellular life functions. As a streamlinedversion of a genome, a basic genetic operating system also is a simplerand more efficient genome because it lacks unwanted or unnecessarygenetic information or nucleic acid structure.

[0054] As a streamlined copy of genes that are obligatory to sustainrudimentary or foundational functions of cellular life, a basic geneticoperating system constitutes a minimal compilation of genes that arerequired for the biosynthesis and maintenance of cellular lifefunctions. Cellular life functions include, for example, viability,replication, transcription, translation, cell division, energygeneration, cellular homeostasis, adhesion, motility migration,environmental adaption, chemotaxis and immune and effector cellresponses. Therefore, a basic genetic operating system can, by itself,substitute for, or function as, a cellular or nanomachine genome.However, and as described further below, a basic genetic operatingsystem also can be combined with other genes and gene sets to augmentthe genetic instructions of the basic operating system. Inclusion ofother genes and gene sets can, for example, additionally enable a hostnanomachine to perform and maintain a wide variety of biochemicalactivities and operations in conjunction with those constitutingfundamental cellular life functions.

[0055] One fundamental cellular life function is viability. A minimalgene set sufficient for viability includes, for example, genes that fallwithin a number of functional categories. Genes within each functionalcategory can be grouped, for example, based on functional independencerelative to another category as well as based on simplicity ofdescription. However, those skilled in the art will understand thatfunctional categories described herein also can be interrelated orinterdependent for performance or maintenance of a nanomachine cellularlife function. For example, genes within a minimal gene setcorresponding to the functional category of transcription can beindependent with respect to genes within the functional category of anaerobic metabolism because a nanomachine can produce a nucleic acid geneproduct using energy sources derived from aerobic pathways. For example,glycolysis, pyruvate dehydrogenase and the pentose phosphate pathwaysare pathways within an aerobic functional group that can generate, forexample, ATP as an energy source in the absence of an aerobicrespiration. Similarly, transcription can be independent with respect toaerobic metabolism when fundamental genes for anaerobic pathways arepresent to produce energy sources. Interrelated functional groups caninclude, for example, transcription and translation. Although both ofthese functional categories can operate independently, both also requirethe gene products of the other category to persistently maintainfunction and homeostasis. The constituent genes and gene products andtheir interrelationships or independence with respect to otherfunctional categories and cellular life functions is described furtherbelow.

[0056] Functional categories of genes within a minimal gene setconstituting the genetic programming sufficient to support viability asa cellular life function include, for example, about nine or lessfundamental biochemical processes. Although interrelated, these processfall under the general groupings of biosynthetic, metabolic andhomoeostatic processes. The biosynthetic groupings include, for example,the functional categories of transcription and translation.

[0057] The metabolic processes include, for example, energy metabolism,carbohydrate metabolism, central intermediary metabolism and nucleotidemetabolism. Energy metabolism can further include the functionalcategories of aerobic metabolism and anaerobic metabolism. Glycolysis,pyruvate dehydrogenase and the pentose phosphate pathways are specificbiochemical pathways supplying high free energy molecules such as ATP,NADH and NADPH under aerobic conditions. Some of these pathways, such asglycolysis, for example, also synthesize high free energy moleculesunder anaerobic conditions. The reductive citric acid cycle is aspecific biochemical pathway supplying high free energy molecules underanaerobic conditions.

[0058] Function categories within the homoeostatic processes include,for example, transport and binding proteins, and housekeeping functions.

[0059] Those skilled in the art will know what fundamental genes are, orcan be, contained within each category, including for example, thosederived from procaryotic and eucaryotic sources. Exemplary listings offunctional categories and constituent minimal gene set sufficient for abasic genetic operating system to direct autonomous nanomachineviability is shown in FIG. 1 and Table 4. Therefore, the functionalcategories constituting a minimal gene set sufficient for a cellularlife function such as viability can be derived from a single species ormultiple species. Similarly, fundamental genes determine to fall withina functional category also will include, for example, functionalequivalents such as orthologs and nonorthologous displacements as wellas functional fragments thereof.

[0060] Various combinations and permutations of functional categories,for example, such as those shown in FIG. 1 and Table 4 for a basicgenetic operating system programmed to direct autonomous nanomachineviability as a cellular life function can be produced depending on theneed and desired operation of the host nanomachine. For example, ananomachine can be programmed to function under completely anaerobicconditions. In this specific example, the functional category specifyinggenes required for aerobic metabolism, which do not substantiallyoverlap with fundamental genes for anaerobic metabolism, can be omittedfrom the basic genetic operating system. Alternatively, the functionalcategory specifying non-overlapping genes required for anaerobicmetabolism can be omitted for a nanomachine programmed to function underaerobic conditions. Similarly, a nanomachine can be programmed togenerate macromolecules, such as nucleotides, by de novo biosynthesis.For the specific example of de novo nucleotide biosynthesis, the salvagepathway genes shown in FIG. 1, for example, can be substituted for apartial or complete set of genes specifying de novo nucleotidebiosynthesis. Further, for example, if a nanomachine of the invention isdesired to chemotax to perform a targeted application, then thisfunctional category and its constituent fundamental genes can beincluded within a basic genetic operating system of the invention.

[0061] Numerous other combinations, substitutions and permutations offunctional categories can be made in a basic genetic operating system ofthe invention to tailor the performance of an autonomous nanomachine toa particular application. Such other modifications of functionalcategories include, for example, anaerobic metabolic pathways,fermentation, stress related genes such as heat shock, DNA repair, RNAprocessing, secretion, glycosylation, glycoside synthesis and isoprenoidsynthesis. Those skilled in the art will know which functionalcategories can be combined, modified or substituted to accomplish apredetermined activity, cellular life function or application.Additionally, as with the other functional categories, the genes withina particular biosynthetic pathway are well know to those skilled in theart. Similarly, using the teachings and guidance provided herein, thoseskilled in the art will know, or can determine, which genes within abiochemical pathway or physiological process are fundamental genes andincluded with a minimal gene set and which genes are dispensable to theefficient function and operation of a genetically programmed cellularlife function.

[0062] A minimal gene set will include, for example, genes within afunctional category that are fundamental to a biochemical process.Fundamental genes include those genes that are essential to the process,without which the activity cannot occur. Fundamental genes also include,for example, those elementary genes that augment the performance of abiochemical process to levels comparable to a cellular life form orcomparable to a reference standard that is required for a targetedapplication. For example, fundamental genes required for proteinsynthesis can include all essential and elementary genes that arenecessary for nanomachine protein synthesis to occur at a ratecomparable to a procaryotic or eucaryotic cell system. Alternatively, ifa targeted application can be accomplished by nanomachine proteinsynthesis rates less than comparable cellular levels, then the requiredfundamental genes can exclude some or all of the elementary genes andstill be considered a minimal gene set, and therefore, a basic geneticoperating system of the invention.

[0063] Those skilled in the art will know, or can determine, theperformance of a biochemical process which constitutes activity levelscomparable to similar processes of a cellular life form or comparable toa reference standard that is required for a targeted application. Aspecific example of a comparable cellular activity level includesprotein synthesis rate under specified environmental, physiological orculture conditions. A specific example of a comparable referencestandard includes accumulated protein synthesis of a specified geneproduct under specified environmental, physiological or cultureconditions sufficient to achieve a predetermined target end point. Suchend point standards can include, for example, accumulation of apredetermined amount of gene product or achievement of a specifiedactivity, such as binding inhibition or regulation of a target molecule.Essentially any nanomachine activity, process, cellular life function,operation or attribute encoded by a minimal gene set will have acorresponding cellular life or reference comparison. Using the teachingand guidance provided herein, those skilled in the art will know, or canroutinely determine, such cognate comparisons between nanomachinesprogrammed by a basic genetic operating system of the invention andeither procaryotic or eucaryotic cellular life forms.

[0064] Similarly, those skilled in the art will know, or can determine,fundamental genes that encode either an essential function or anelementary function within a minimal gene set. For example, an essentialgene is indispensable to a cellular life function of a nanomachine andis therefore required to be encoded by a basic genetic operating systemprogrammed for the reference life function. Specific examples ofessential genes include those coding for RNA polymerase subunits.Related to essential genes are those that perform elementary or basalfunctions which can augment an activity of an essential gene or its geneproduct. As such, an elementary gene is dispensable but only at asubstantial cost to basic nanomachine operation. A specific example of afundamental gene encoding an elementary function includes genes codingfor transcription factors such as transcription terminators. Removal ofa transcription terminator from a basic genetic operating system doesnot substantially affect viability of a host nanomachine, althoughinclusion would augment at least resource utilization.

[0065] Those skilled in the art will understand that augmentation of aelementary process differs from optimization. The former referring tosupplementation of a fundamental process encoded by a basic geneticoperating system, whereas the latter refers to a substantial enhancementof fundamental processes or of overlying activities and functionsadditional to minimal gene set activities. Substantial enhancements caninclude, for example, the inclusion of multiple polypeptide species orisotypes, such as those related within a family, that each performspecialized, but related, subfunctions within a broader activityspectrum. Generally, substantial enhancements of a fundamental processcan be categorized as gene or functional redundancy of a componentmolecule or functional category encoded by a basic genetic operatingsystem.

[0066] A nanomachine of the invention is autonomous when, for example,it is capable of independently carrying out its cellular life functionestablished by the nucleic acid programming contained within its basicgenetic operating system. Similarly, a nanomachine activity or operationalso can be considered as autonomous when, for example, the activity oroperation can be performed independently due to instructions establishedby the nanomachine's basic genetic operating system. For example, ananomachine of the invention is autonomous when it can execute itsprogrammed function as engineered. Therefore, autonomy refers to theability of a nanomachine to synthesize, perform, and maintain, forexample, all molecules, activities, and processes that are engineeredthrough nucleic acid coding and regulatory sequences into a basicgenetic operating system of the host nanomachine.

[0067] For example, if a basic genetic operating system is designed tobe a complete set of genetic instructions for glycolysis, then anautonomous nanomachine can metabolize glucose to its end products. Incontrast, for example, a nanomachine can still be considered to beautonomous where its basic genetic operating system has a designeddefect in the glycolysis gene set and where a glycolytic intermediatedownstream from the designed defect can be exogenously supplied.Addition of the downstream intermediate allows the nanomachine tocontinue self-production of its encoded activities and operationsdespite having an incomplete gene set. Therefore, dependence on externalor exogenous sources of required molecules that could be encoded into abasic genetic operating system of the invention does not precludeautonomy of a nanomachine so long as the basic genetic operating systemhas been engineered for such a predetermined dependence.

[0068] Similarly, a nanomachine of the invention is considered to beprototrophic when, for example, its basic genetic operating systemcontains a complete minimal gene set for an engineered cellular lifefunction, activity or operation. A complete minimal gene set orfunctional category of fundamental genes includes, for example, thosegenes which are adequate for a host nanomachine to execute and maintainthe engineered cellular life function, activity or operation in aself-sufficient manner. Therefore, a basic genetic operating systemengineered for prototrophic functions and activities will be autonomousfor the referenced function without requirements for exogenoussupplementation of a deficient gene product in the minimal gene set orreferenced functional category.

[0069] In comparison, a nanomachine of the invention is considered to beauxotrophic when, for example, its basic genetic operating systemcontains a designed gene deficiency in an otherwise complete minimalgene set. For example, an auxotrophic basic genetic operating systemcontains an incomplete minimal gene set for an engineered cellular lifefunction, activity or operation. To be auxotrophic, however, anincomplete minimal gene set or functional category of fundamental geneswill, for example, be able to be execute and maintain its engineeredfunction with exogenous supplementation of a gene product of thedesigned gene deficiency. Similarly, an auxotrophic basic geneticoperating system also can execute and maintain its engineered functionwith exogenous supplementation of a component downstream or functionallyequivalent to the designed defect. Therefore, autonomy of auxotrophicsystems of the invention are rescuable by design through the addition ofan auxotrophic biomolecule. As such, a basic genetic operating systemengineered for auxotrophic functions and activities will be autonomousfor the referenced function with the exogenous supplementation of anengineered deficient gene product or a component that can rescue thedesigned deficiency.

[0070] The functional categories constituting a basic genetic operatingsystem of the invention can be arranged in essentially any desiredphysical or functional order so long as all genes of the minimal geneset are present and operative. However, arranging the functionalcategories in relative order of importance can augment the efficiency ofthe host nanomachine operation. Similarly, arranging the functionalcategories in relative order of importance also can increase the qualityof a particular nanomachine product or activity. Depending on thedesired use of a nanomachine of the invention, the functional genecategories can be selectively arranged to optimize, for example, thegenetic programming of the basic genetic operating system, nanomachineoperation efficiency or genome size.

[0071] One arrangement of functional categories within a basic geneticoperating system conferring viability on a host nanomachine can be, forexample, in the relative order of gene product use to achieve aprogrammed cellular life function. To sustain cellular life, ananomachine should be able to biosynthesize component macromolecules. Assuch, one relative order of use can follow, for example, the normalinformation to product flow of a cell, which would be from transcriptionof the genome to translation of the mRNA into polypeptide products. Thisorder has the advantage in that genes encoding precursors andintermediates to the working nanomachine products are produced first,thereby preventing rate limiting steps in the production and activity ofcentral nanomachine components. Therefore, a relative order offunctional categories for efficient nanomachine operation can be genesconstituting transcription and translation categories, respectively,followed by functional categories specifying nanomachine energy sources.Such energy sources can be fundamental gene sets sufficient for eitheror both aerobic metabolism and anaerobic metabolism. Additionally,pathways specifying energy sources also can be ordered relative to theiruse in cellular metabolism. For example, fundamental genes encoding theglycolysis pathway can be placed in a relative order within a basicgenetic operating system earlier than genes specifying the pyruvate orpentose phosphate pathways, or earlier than non-fundamental genes suchas those specifying the citric acid (TCA) cycle or the reductive citricacid cycle.

[0072] The remainder of the functional categories of genes sufficient tosupport viability, for example, of a host nanomachine can be inessentially any desired order depending on the targeted application ofnanomachine and desired efficiency. One exemplary order of the remainingcategories can be, for example, carbohydrate metabolism, centralintermediary metabolism, nucleotide metabolism, transport and bindingproteins, and housekeeping functions, respectively. The number ofpermutations and combinations of functional category order are many.Those skilled in the art will know what order and combination offunctional categories can be made within a basic genetic operatingsystem to achieve a desired result.

[0073] Ordering of functional categories can be based on severaldifferent criteria. For example, ordering can be accomplished withreference to physical order or temporal order. Any particular physicalorder can be accomplished by the architectural design and placement of aminimal gene set within a basic genetic operating system. Additionally,physical order can be with reference to any of a number of genomicmarkers. Such markers include, for example, an origin of replication, aparticular gene or a particular gene set. Specific examples of orderingfunctional categories within a basic genetic operating system relativeto a gene or gene set includes placing the first ordered functionalcategory next to an expression cassette for the production of abiomolecule, or next to an indispensable gene set such as that foraerobic metabolism. Similarly, functional category ordering can be, forexample, unidirectional, bidirectional, with respect to a single strandof the genome, with respect to both stands of the genome and allcombinations thereof. Utilizing both strands of the genome has theadvantage of efficient use of genome space.

[0074] Any particular temporal order can be accomplished, for example,by activation and repression of targeted genes and gene sets in aselected order. Selective activation and repression can be achieved, forexample, by cis and trans acting factors or by conditional regulation oftranscription or translation. Therefore, any desired temporal order ofexpression of functional categories or of their constituent fundamentalgenes can be achieved by selective activation of their respectivepromoters. Selective activation can be achieved by, for example,positive regulation or derepression of an inhibitor. The cis andtransacting factors used for such selective activation can be, forexample, either homologous or heterlogous elements or factors comparedto the gene it regulates. Additionally, temporal order of expressionalso can be accomplished by a combination of selected activation andrepression of genes and gene sets and physical order of particulartarget genes or their trans acting regulators. Other methods, well knownto those skilled in the art for controlling the relative order ofexpression of functional categories or constituent fundamental genesinclude, for example, RNA processing, post-translational modificationssuch as phosphorylation, glycosylation, proteolytic cleavage, signaltransduction cascades and clotting cascades.

[0075] Therefore, the invention also provides a basic genetic operatingsystem for an autonomous prototrophic nanomachine that encodes a minimalgene set sufficient for viability which directs synthesis of functionalcategories in a relative order consisting of transcription, translation,aerobic metabolism and glycolysis/pyruvate dehydrogenase/pentosephosphate pathways. The relative order can be, for example, withreference to physical or temporal arrangement of functional categories.

[0076] Also provided is a basic genetic operating having a minimal geneset that is devoid of at least one gene selected from the groupconsisting of MG008, MG009, MG056, MG221, MG332, MG448 or MG449, anortholog or a nonorthologous gene displacement thereof.

[0077] Although conserved genes between, for example, M. genitalium andH. influenza, the above genes are redundant in structure or functioncompared to other genes found within these and other species genome. Forexample, MG008 encodes furan and thioprene oxidase. MG262 encodes anexonuclease. MG009, MG056, MG221, and MG332 encode polypeptides withnucleotide binding domains such as ATP-, GTP-, NAD, FAD and SAM-bindingdomains, a permease or other conserved domains. MG448 and MG449 encodepolypeptides with chaperone binding domains. Additionally, some of thesegenes are unnecessary for rudimentary functions and therefore moreappropriate to be placed in an overlying genetic program operated from abasic genetic operating system of the invention. For example, thosegenes encoding chaperone and permease functions are not necessarilyrequired for autonomous nanomachine operation.

[0078] The invention further provides a basic genetic operating systemfor a nanomachine genome that is sufficient for viability having lessthan about 140 kilobases (kb) in size. The basic genetic operatingsystem can be about 152 or less fundamental genes, functional fragments,orthologs or nonorthologous displacements thereof.

[0079] A basic genetic operating system containing a minimal gene setsufficient for viability can be constructed to be any size so long as itcan be packaged into a particle envelope or other partitioningstructure. One advantage of engineering a basic genetic operating systemis that it is a bottom-up approach to construction of the nanomachinegenome. Similar to bottom-up nanomachine construction through biologicalself-assembly of matter at the atomic and molecular level, designing aminimal gene set specifying predetermined functions allows, for example,precise structures to be designed and synthesized. For example, genescan be arranged to conserve space by juxtaposition of fundamental geneswith minimal inclusion of intervening genomic sequence. Regulatoryregions such as enhancers can be moved from intergenic regions tointrons, for example. Similarly, non-useful nucleic acid segments canbe, for example, truncated or otherwise omitted, structural genesequences such as introns, 5′ and 3′ gene flanking regions anduntranslated sequences can be reduced or eliminated, genes can beoverlapped or incorporated into genes transcribed and translated aspolycistronic mRNA, and the primary sequence can be modified toincorporate optimal nucleotide usage to increase efficiency intranslation of transcribed mRNA. Additionally, fundamental genesconstituting a minimal gene set can be, for example, tailored to includeonly relevant functional domains. Therefore, a minimal gene set canconsist of functional fragments of some or all of the fundamental genesthat constitute one or more functional categories.

[0080] Those skilled in the art will know, or can readily design, giventhe teachings and guidance provided herein, a wide range of sizes for abasic genetic operating system sufficient to support a cellular lifefunction such as viability. For example, a minimal gene set such as thatshown in FIG. 1 or corresponding orthologous genes set forth in Table 4which are sufficient to specify nanomachine viability, can be organizedinto a basic genetic operating system of about 140 kilobase (kb) pairsor less. For example, juxtaposition of intronless versions of thesegenes can result in a nucleic acid of about 137,589 base pairs (bp).Such a minimal gene set encodes about 152 fundamental genes for a totalof about 45,863 amino acids. Inclusion of naturally occurring expressionand regulatory elements, heterologous elements or combinations thereof,in a juxtapositional arrangement can be accomplished with minimalincrease in nucleic acid size as these elements contribute minimally tooverall size of the basic genetic operating system compared to thefundamental genes of the minimal gene set.

[0081] The size of a basic genetic operating system additionally can bereduced by, for example, employing any or various combinations of thearchitectural designs described above. For example, coding regions,noncoding regions, expression and regulatory sequences can be partiallyor substantially overlapped between some or all of the genesconstituting a minimal gene set specifying a cellular life function orgenes within one or more functional categories. Additionally, theconstituent fundamental genes can be arranged on both strands of adouble stranded nucleic acid to further condense a basic geneticoperating system of the invention. Therefore, a basic genetic operatingsystem of the invention programming non-replicative cellular lifefunctions of a nanomachine can be substantially smaller than about 140kb. For example, a basic genetic operating system sufficient forviability can be about 130 kb or less, 120 kb or less 110 kb or less andeven 100 kb or less. It is also possible to reduce in half the size ofsuch basic genetic operating systems to about 70 kb by, for example,substantial overlap and truncation of fundamental genes thatconstituting a minimal gene set. Other architectural designs well knownto those skilled in the art similarly can be used to condense oroptimize the structure of a basic genetic operating system of theinvention.

[0082] A basic genetic operating systems of the invention also caninclude, for example, various structural features that facilitate thetransfer of information into encoded polypeptides and the operation ofcellular life functions of a nanomachine. Such structural features caninclude, for example, nuclear or cell membrane binding sites, bindingregions for chromosome scaffolding, histone binding regions forchromosome condensation and, for example, non-coding intergenic nucleicacid. The presence of such intergenic spacer segments can allow, forexample, efficient entry and exit of nucleic acid binding factors byreducing steric hindrance, binding site competition and topologicalconstraints, for example. Additionally, the basic genetic operatingsystems of the invention can be designed as double stranded or singlestranded genomic structures. Those skilled in the art will know which ofvarious structural regions can be incorporated into a basic geneticoperating system to achieve a targeted application as well as toincrease or optimize its performance as a nanomachine genome. Forexample, if the nanomachine is to parallel procaryotic cellular lifeforms, then chromosome condensation is not necessarily important.However, chromosome condensation, anchorage and scaffolding can beadvantageously utilized in basic genetic operating system that specifiesfundamental genetic programming for higher eucaryotic cellular lifeforms.

[0083] As described above, a basic genetic operating system specifyingbasal cellular life functions such as viability can be accomplished, forexample, with about 152 fundamental genes or less. They can be grouped,for example, in about 9 functional categories. The number of constituentgenes within each functional category can vary, for example, dependingon the targeted application of the host nanomachine. For example, thenumber of constituent genes can vary depending on whether theprogramming is for de novo or salvage pathway biosynthesis of a moleculeor class of molecules. The number of constituent fundamental genes alsocan vary, for example, depending on whether the programming specifiesviability within an intracellular or extracellular physiologicalenvironment or an extracellular non-physiological environment.Constituent fundamental genes also can vary depending on whether theprogramming specifies aerobic or anaerobic gene products for productionof energy sources. Inclusion of membrane sorting, polypeptide secretionand intracellular trafficking and vesicle gene functions also can varythe number of constituent fundamental genes within a functionalcategory. Similarly, and as described further below, the number ofconstituent genes within each functional category can vary, for example,depending on whether the basic genetic operating system specifiesprototrophic or auxotrophic nanomachine autonomy. As set forth in Table4 the number of constituent gene products also can vary depending onwhether the basic genetic operating system is engineered fromprocaryotic or eucaryotic genes, orthologs or nonorthologousdisplacements thereof.

[0084] Generally, however, constituent genes sufficient to supportviability can be grouped, for example, into about 14 genes in atranscription gene category, about 90 genes in a translation genecategory, about 13 genes in an aerobic metabolism gene category, about16 genes in a gene category constituting glycolysis, pyruvatedehydrogenase, and pentose phosphate pathways, about 3 genes in acarbohydrate metabolism gene category, about 3 genes in a centralintermediary metabolism gene category, about 2 genes in a nucleotidemetabolism gene category, about 10 genes in a transport/binding proteingene category and about 1 genes in a housekeeping function genecategory. The category containing genes functioning in translationprocesses also can be further divided, for example, into two furthersubgroups. These translation subgroups can consist of about 13 geneswhose gene products function in polypeptide modification and translationfactors and about 52 genes whose gene products function in ribosomebiosynthesis, assembly and modification. Similarly, there are about 10fundamental genes encoding glycolytic functions, about 2 fundamentalgenes encoding pyruvate dehydrogenase pathway gene products and about 4fundamental genes encoding gene products that function in the pentosephosphate pathways.

[0085] Exemplary fundamental genes and their gene product functionswithin each of the above functional categories and subgroups are shownin FIG. 1. Orthologous genes which can similarly substitute for thoseshown in FIG. 1 are set forth in Table 4 below. Given the teachings andguidance provided herein those skilled in the art will know or candetermine, by for example, comparative genomics and gene productfunction, other orthologs or nonorthologous displacements that similarlycan substitute for one or more of the fundamental genes shown in FIG. 1or Table 4. Therefore, the invention provides a basic genetic operatingsystem sufficient to direct autonomous prototrophic viability of a hostnanomachine having about 152 or less fundamental genes that consists ofsubstantially the same fundamental genes show in FIG. 1, Table 4,including orthologs or nonothorologous displacements thereof.

[0086] Although the invention has been described with reference to basicgenetic operating system encoding a minimal gene set sufficient forviability, those skilled in the art will know that various other basicgenetic operating system programming other cellular life functions canbe engineered and synthesized given the teachings and guidance providedherein. For example, described further below are basic genetic operatingsystems encoding replication functional categories so as to conferreplication competence as a cellular life function of a hostnanomachine. Additionally, a basic genetic operating system can beengineered for autonomous nanomachine operation in an intracellularenvironment, such as is the case for M. genitalium, or an extracellularenvironment such as is the case from H. influenza, E. coli, otherprocaryotic cells and eucaryotic cells. Further non-replicative basicgenetic operating systems can additionally include, or programmingchanged to encode, other cellular life functions such as polypeptidesynthesis, membrane integrity, polypeptide folding, polypeptidetrafficking, extracellular synthesis and transport, motility,fermentation and spore formation.

[0087] For example, protein synthesis machinery can be encoded in theabsence of transcription functions for specific mRNA species. A hostnanomachine can be supplied with exogenous mRNA for synthesis of one ormore encoded polypeptides. Also a basic genetic operating system caninclude membrane structural genes, integral membrane or transmembranepolypeptides that augment the structural integrity of a lipid membraneparticle envelope. In like fashion, polypeptide folding functions andtrafficking functions can be encoded. For example, sec-dependentpolypeptide secretion in procaryotes and signal recognition particle(SRP)-dependent tranaslocation in eucaryotes are two specific examplesof folding and trafficking functions. Specific examples of extracellularsynthesis and transport can be useful for nanomachine survival incertain environments and include, for example, translocation ofmolecules using ABC transporters, synthesis of glycogen, synthesis andsecretion of glycopolymers such as dextrans and xanthan gum.

[0088] Additionally, selected pathways for aerobic energy production oranaerobic energy functions such as genes encoding the reductive citricacid cycle can be programmed. Briefly, the carbohydrate pathways foraerobic energy production can include, for example, glycolysis, thepentose phosphate pathway and the Entner-Doudoroff pathway. Glycolysis,or the EMP pathway is present in both procaryotic and eucaryoticorganisms and functions to oxidize carbohydrate to pyruvate and tophosporylate ADP. This pathway also provides precursor metabolites forother pathways, including feeding into the pentose phosphate pathway viaglucose-6-phosphate. The pentose phosphate pathway is similarly presentin both procaryotic and eucaryotic organisms and produces NADPH, pentosephosphates, which are precursors to ribose and deoxyribose, anderythrose phosphate, which is a precursor to aromatic amino acids,phenylalanine, tyrosine and tryptophan, and phoshoglyceraldehyde. TheEnter-Doudoroff pathway is found generally in procaryotic organisms andproduces various energy molecules in the presence of specific carbonsources, such as gluconic acid.

[0089] Other aerobic energy functions include, for example, the pyruvatedehydrogenase complex and the Citric Acid Cycle. Pyruvate dehydrogenasecomplex is an enzyme located in the cytosol of procaryotes and in themitochondria of eucaryotes. This complex functions to decarboxylatepyruvate to acetyl-CoA, CO₂ and NADH. Acetyl-CoA can enter the citricacid cycle, where it is oxidized to CO₂. The Citric Acid Cycle operatesin conjunction with repiration to oxidize NADPH and FADH₂ and generallyfunctions during aerobic growth. Under anaerobic conditions, procaryoteshave a modified pathway called the reductive citric acid pathway whereNADH is oxidized by an organic acceptor that is generated duringcatabolism.

[0090] Anaerobic energy production includes, for example, including orsubstituting for pyruvate dehydrogenase, fundamental genes encodingpyruvate-ferredoxin oxidoreductase or pyruvate-formate lyase, whichfunction to breakdown pyruvate into acetyl-CoA under anaerobicconditions. Utilization of the reductive citric acid pathway will allowfermentation for example. Although not present in M. genitalium, thesefunctions can be obtained from genes in other organisms such as E. coli.Briefly, to obtain anaerobic respiration, α-ketoglutarate dehydrogenaseactivity can be down regulated or the gene rendered non-functional, andfumarate reductase can replace, or be additionally included with,succinate dehydrogenase.

[0091] Further, fermentation cycles such as butyrate or butanol-acetonefermentation from C. acetobutyliciuum also can be programmed. Basicmotility functions can be changed by encoding different flagella motorsto be compatible, for example, with the host nanomachine environment.Such different flagella also can include a lipopollysaccharide sheath orbe a spirochete flagella, for example. Spore forming functions can beincluded from organisms such as B. subtilis and can include genes suchas SpoOA, SpoOF, KinABC and others. Other basic cellular life functionsalso are well known to those skilled in the art and can be included in abasic genetic operating system of the invention.

[0092] Any basic genetic operating system of the invention can besupplemented with additional genetic programming to, for example,supplement fundamental nanomachine activities or operation, or, forexample, to customize a host nanomachine to perform essentially anydesired function. Supplementation with additional genetic programmingcan include, for example, basic genetic operating systems containingfundamental programs specifying, for example, prototrophic autonomousfunctioning, auxotrophic autonomous functioning, non-replicativecellular life functions and replication competent cellular lifefunctions. Such additional genetic programming can be conceptuallyanalogized to computer application programs overlaid on, or run off of acomputer operating system, where the latter can be conceptuallyanalogized to a basic genetic operating system of the invention. Byanalogy, a basic genetic operating system of the invention can beengineered to contain controlling functions, nucleic acid sequences andnucleic acid structures for entry and execution of genetic subroutinescontaining instructions for any desired cellular life function,biochemical activity or operation. Such additional genetic programmingcan be simple, such as inclusion of an expression cassette for one ormore gene products to be produced by the host nanomachine, or complex,such as inclusion of an entire biochemical pathway or network to confersophisticated physiological responses. Therefore, the host biologicalnanomachines of the invention can be designed and tailored to performone, two, several and even many additional activities and operations upto and including substantial functional mimicry of naturally occurringcellular life forms.

[0093] Additional genes that can be included can be obtained from anyfunctional category, including those that constitute a minimal gene setas well as those which substantially enhance the functioning andoperation of a host nanomachine. Such additional categories include, forexample, those set forth in FIG. 1 for non-replicative basic geneticoperating systems, FIG. 2 for replication competent basic geneticoperating systems, orthologs for genes within these functionalcategories as exemplified in Table 4, or as known to those skilled inthe art and nonorthologous displacements. Therefore, a basic geneticoperating system sufficient for viability, other non-replicativecellular life functions, replication competence or other replicationcompetent cellular life functions, for example, can be furthersupplemented with overlying genetic applications encodingnon-fundamental genes for these referenced cellular life functionswithin any of the functional categories show, for example, in FIGS. 1 or2. Specifically, overlying genetic applications can contain, forexample, non-fundamental genes within the functional categories forreplication, transcription, translation, the various metabolicfunctional categories, a phosphotransferase system (PTS) category, asignal transduction and regulation category, a transport and bindingprotein category, a particle division category, a chaperone systemcategory, a particle envelope category and a housekeeping functioncategory. Other non-fundamental genes and functional categories wellknown to those skilled in the art also can be included in suchsupplemental programming to confer one or more predetermined activitiesonto a host nanomachine of the invention.

[0094] Specific examples of non-fundamental genes within the abovefunctional categories include, for example, genes selected such as theM. genitalium genes termed MG020, MG022, MG034, MG039, MG041, MG046,MG051, MG061, MG062, MG108, MG121, MG129, MG183, MG188, MG368, MG429, anortholog or a nonorthologous gene displacement thereof. MG020 and MG183encode, for example, genes involved in amino acid metabolism. MG022encodes a gene involved in transcription. MG034 and MG051 encodes a geneinvolved in nucleotide metabolism. Nine of the above genes encodeactivities required for the PTS system. These genes include, forexample, MG039, MG041, MG061, MG062, MG108, MG121, MG129, MG188 andMG429. MG046 is involved, for example, in secretion and therefore, canbe considered to fall within the translation functional category.Finally, MG368 encodes a gene involved in lipid metabolism. Numerousother genes also exist from both procaryotic and eucaryotic cells andorganisms. Any other genes within functional categories of a basicgenetic operating system of the invention also can be integrated into abasic genetic operating system to generate a nanomachine genome encodinga specified activity or operation additional to that encoded by itsbasic genetic operating system.

[0095] Similarly, a basic genetic operating system sufficient forviability or replication competence, for example, also can be integratedby genetic applications programing independent or substantiallyindependent functions to those specified in the underlying operatingsystem. For example, complete pathways and networks for variousphysiological functions can be incorporated, including for example,motility, chemotaxis, homing, apoptosis, cellular immunity, humoralimmunity, innate immunity, cytokine production, growth factorproduction, cellular adhesion and cellular migration. Other activitiesthat can be integrated with a basic genetic operating system caninclude, for example, drug resistance, drug sensitivity, temperature, pHand salimity resistance or sensitivity as well as modulation of a redoxstate. Additional genes within any of the fundamental categories such astranscription or translation can be added as well as genes encodingpost-translational modifications, functions, or polypeptide foldings.Additionally, a basic genetic operating system also can be integratedwith genes encoding structural polypeptides such as cytoskeletal andmembrane skeleton polypeptides to increase structural integrity of ananomachine particle. Numerous other additional programming can beincorporated into a basic genetic operating system of the invention toimpart an attribute or confer an activity onto the host nanomachine.Those skilled in the art will know what additional functions are germaneto a targeted nanomachine application as well as which genes arenecessary or sufficient to accomplish a particular outcome.

[0096] Therefore, the invention provides a prototrophic or auxotrophicbasic genetic operating system having one or more non-fundamental genesoperationally linked to the basic genetic operating system. The basicgenetic operating system can encode non-replicative cellular lifefunctions, including activities sufficient for viability, as well asreplication competent cellular life functions. Such non-fundamentalgenes can be, for example, within a functional category of a basicgenetic operating system or any other gene or genes that are engineeredto impart a predetermined activity, operation or function onto a hostnanomachine of the invention.

[0097] As described above, one particular application that can beadvantageously suited to the bottom-up design and self-synthesis of abasic genetic operating system and host nanomachine, respectively, isthe designed incorporation of biomolecule expression and production. Oneor more expression cassettes, for example, can be engineered into abasic genetic operating system of the invention for modular insertion ofa gene encoding any desired biomolecule. Similarly, insertion of two ormore genes and complete pathways encoding multiple subunits ofbiomolecules, multiple biomolecules or, for example, completebiosynthetic pathways or networks for nanomachine synthesis of one ormore biomolecules of interest can be routinely engineered into a basicgenetic operating system of the invention by those skilled in the art.Expression of such biomolecules can be constitutive or regulated, forexample. Regulated expression can be accomplished by, for example, anygenetic, recombinant, enzymatic or signal transduction mechanism knownin the art, including for example, inducible or conditional expressionby exogenous or physiological stimuli. Therefore, biosyntheticregulation also can be tailored to a particular nanomachine applicationor operation.

[0098] For example, insulin can be a biomolecule produced by ananomachine of the invention. The insulin can be constitutively producedif it is desirable to make pharmaceutical quantities ex vivo.Alternatively, a nanomachine can be engineered with an inducibleexpression elements that is activated by elevated glucose levels or canbe activated with an exogenously administered modulator. As describedfurther below, such nanomachines can be advantageously administered todiabetic individuals for the treatment of diabetes.

[0099] Biomolecules can include, for example, a therapeuticmacromolecules such as a polypeptide, a polypeptide complex, aribo-(RNA) or deoxyribonucleic acid (DNA), lipid, sugar,glycopolypeptide, glycoside polypeptide, polyketides as well asbiosynthesizable organic compounds. Such organic compounds can include,for example, macromolecule building block monomers such as amino acids,purine and pyrimidine bases, nucleosides, nucleoside monophosphates, andnucleotides, aldehydes, ketones, fatty acids, sugars, steroids,hydrocarbons, polymers, alkaloids, hormones, cytokines, chemokines,cofactors, neurotransmitters and the like. Biomolecules also can be, forexample, macromolecules or biosynthesizable organic compounds suitablefor diagnostic or industrial applications.

[0100] The basic genetic operating systems of the invention, including,for example, non-replicative and replication competent forms, can beproduced by any method of nucleic acid synthesis known to those skilledin the art. Such methods include, for example, chemical synthesis,recombinant synthesis, enzymatic polymerization and combinationsthereof. These and other synthesis methods are well known to thoseskilled in the art.

[0101] For example, methods for synthesizing oligonucleotides can befound described in, for example, Oliqonucleotide Synthesis: A PracticalApproach, Gate, ed., IRL Press, Oxford (1984); Weiler et al., Anal.Biochem. 243:218 (1996); Maskos et al., Nucleic Acids Res. 20(7):1679(1992); Atkinson et al., Solid-Phase Synthesis ofOligodeoxyribonucleotides by the Phosphitetriester Method, inOligonucleotide Synthesis 35 (M. J. Gait ed., 1984); Blackburn and Gait(eds.), Nucleic Acids in Chemistry and Bioloqy, Second Edition, NewYork: Oxford University Press (1996), and in Ansubel et al., CurrentProtocols in Molecular Biology, John Wiley and Sons, Baltimore, Md.(1999).

[0102] Recombinant and enzymatic synthesis, including polymerase chainreaction and other amplification methodologies can be found describedin, for example, Sambrook et al., Molecular Cloning: A LaboratoryManual, Third Ed., Cold Spring Harbor Laboratory, New York (2001) and inAnsubel et al., (1999), supra.

[0103] Solid-phase synthesis methods for generating arrays ofoligonucleotides and other polymer sequences can be found described in,for example, Pirrung et al., U.S. Pat. No. 5,143,854 (see also PCTApplication No. WO 90/15070), Fodor et al., PCT Application No. WO92/10092; Fodor et al., Science (1991) 251:767-777, and Winkler et al.,U.S. Pat No. 6,136,269; Southern et al. PCT Application No. WO 89/10977,and Blanchard PCT Application No. WO 98/41531. Such methods includesynthesis and printing of arrays using micropins, photolithography andink jet synthesis of oligonucleotide arrays.

[0104] Methods for synthesizing large nucleic acid polymers bysequential annealing of oligonucleotides can be found described in, forexample, in PCT application No. WO 99/14318 to Evans and also describedfurther below in the Examples. All of the above references areincorporated herein by reference in their entirety.

[0105] The invention additionally provides an autonomous prototrophicnanomachine having a basic genetic operating system for autonomousprototrophic viability and a particle envelope.

[0106] Any of the basic genetic operating systems described above, suchas those directing the synthesis and maintenance of basic cellularviability functions can be packaged into a particle envelope to producean autonomously viable prototrophic nanomachine of the invention.Particle envelopes can include, for example, any semi-permeablepartitioning biocompatible material that maintains separation of thebasic genetic operating system or nanomachine genome, nanomachinemacromolecular structures such a ribosomes and transcriptionalapparatus, macromolecules and organic molecules from the externalenvironment. A particle envelope can allow, for example, by diffusion,passive or active transport, pinocytosis, phagocytosis, vesicle fusionor other processes well known to those skilled in the art, the influx ofnutrients, minerals and other molecules needed for the properfunctioning and operation of the nanomachine. Similarly, a particleenvelope can allow by, for example, the above processes well known inthe art, the efflux of metabolic by-products and waste products.

[0107] Various biocompatible materials well known to those skilled inthe art can be used as a particle envelope. For example, a particleenvelope can be a lipid vesicle or a lipid bilayer similar to naturallyoccurring cellular membranes. Other biocompatible materials useful as aparticle envelope include, for example, phospholipids, liposomes,lipoprotein micelles, and viral or phage envelopes. Alternatively,particle envelopes can be constructed from synthetic or naturallyoccurring materials such as filter membranes, Gortex™, polyamides,polyfluorenes and fluorocarbons. Combinations of the above biocompatiblematerials also can be used for nanomachine particle envelopes of theinvention. Also, a basic genetic operating system of the invention canfurther be programmed, by inclusion of genes encoding for fatty acid andlipid biosynthesis, for example, to autonomously produce bilayer lipidmembranes similar to naturally occurring cells.

[0108] Initial functional operation of a nanomachine can require, forexample, the inclusion of starter molecules and macromolecules that aresufficient to achieve at least one round of transcription ortranslation. For example, nanomachine particle containing only a basicgenetic operating system without essential cellular machinery,precursors and energy sources to initially transcribe or translate denovo the nanomachine genome can be inoperative. Therefore, startercomponents consisting of, for example, the above machinery, precursorsor energy sources can be packaged within the nanomachine particleenvelope in sufficient amounts to allow genome-directed synthesis andproduction of threshold amounts of nanomachine components. A thresholdamount is an amount that is produced from a basic genetic operatingsystem which is sufficient for autonomous nanomachine activity andoperation. Because macromolecules and organic molecules can have finitehalf-lives, the initially packaged starter components will be exhaustedor cured following initial operation of the nanomachine particle.Therefore, autonomous programmed functions will take over to replenishfundamental components and maintain prototrophic homeostasis of ananomachine of the invention.

[0109] Starter components can be, or obtained from, for example, celllysates, cellular fractions, recombinant production, biochemicallypurification, cellular-nanomachine fusions and other sources and methodswell known to those skilled in the art. Generally, starter componentscan contain threshold amounts of each gene or end product componentsynthesized by a gene, pathway or network within the corresponding basicgenetic operating system. However, nanomachine particles of theinvention can be brought up to operation with only a few rudimentaryactivities and structures such as RNA polymerase, ribosomes andtranslation factors and an energy source. Exemplary amounts of startercomponents include, for example, femtomolar, nanomolar or micromolarquantities of essential fundamental gene products. Those skilled in theart will know that the actual amount and composition of the startercomponents can be adjusted depending on the need. For example,increasing the initial concentration of energy components such as ATPcan allow corresponding decreases in number of different types ofmolecules within the starter composition because the nanomachine willhave a larger initial reservoir before it has to start producing its ownenergy supply.

[0110] The invention further provides a basic genetic operating systemfor an autonomous auxotrophic nanomachine having a nanomachine genomeencoding a minimal gene set sufficient for viability in the presence ofan auxotrophic biomolecule.

[0111] As described previously, basic genetic operating systems that candirect autonomous nanomachine cellular life functions in the presence ofan exogenous supply of a biomolecule are auxotrophic basic operatingsystems and host nanomachines, respectively. The teachings and guidanceset forth above with respect to autonomous prototrophic basic operatingsystems and host nanomachines are similarly applicable to auxotrophicsystems and nanomachines. One difference, however, being that anengineered deficiency is functionally complimented by exogenous suppliesof a biomolecule that can rescue the design defect.

[0112] Therefore, auxotrophic basic genetic operating systems similarlycan include, for example, minimal gene sets encoding the functionalcategories of transcription, translation, aerobic metabolism, anaerobicmetabolism, carbohydrate metabolism, central intermediary metabolism,nucleotide metabolism, transport and binding proteins, and housekeepingfunctions. Such categories can additionally be synthesized in anydesired physical or temporal order including, for example, a relativephysical or temporal order of transcription, translation, aerobicmetabolism and glycolysis, pyruvate dehyrogenase, pentose phosphatepathways, respectively. Similarly, as described in reference to aprototrophic basic genetic operating system sufficient for viability, anauxotrophic basic genetic operating system sufficient for viability alsocan be devoid of at least one gene selected from MG008, MG009, MG056,MG221, MG332, MG448 or MG449, an ortholog or a nonorthologous genedisplacement thereof. Likewise, an auxotrophic basic genetic operatingsystem can similarly be designed as a spatially condensed nucleic acidof about 140 kb or less in size. The design alternatives andconsiderations described previously are also directly applicable toauxotrophic basic genetic operating systems. Similarly, the design andincorporation of additional genetic programming overlaid onto, and runoff of, a prototrophic basic genetic operating system are additionallydirectly applicable to an auxotrophic basic genetic operating system.Therefore, an auxotrophic basic genetic operating system can beengineered to include expression cassettes for the production of one ormore biomolecules, biochemical pathways and networks.

[0113] The invention further provides a basic genetic operating systemfor an autonomous auxotrophic nanomachine having about 151 or lessfundamental genes.

[0114] As described previously, a basic genetic operating systemspecifying basal cellular life functions such as viability can beaccomplished, for example, with about 152 fundamental genes or less.However, for an auxotrophic basic genetic operating system, any one ormore of these genes can be rendered deficient so long as the deficiencycan be complemented or rescued by supplementation with a compound,molecule or macromolecule. Those skilled in the art will know which genefunctions can be supplied by supplementation of the nanomachine externalenvironment. For example, glycolysis metabolizes glucose to glucosephosphate via glucokinase. Elimination of the glucokinase gene can berescued by suppling glucose phosphate rather than glucose in theexternal environment to maintain autonomy of such a system auxotrophicfor glucokinase. Similarly, entire functional systems can be deleted ifthe components are added to the external medium or, alternatively,introduced into the nanomachine itself. For example, elimination ofribosome synthesis and protein synthesis machinery also can be designedinto an auxotrophic basic genetic operating system and these functionscan be rescued by suppling a cell-free or artificial extract to provideprotein synthesis function. Such auxotrophic nanomachines canautonomously function for polypeptide synthesis directed by theauxotrophic basic genetic operating system using the externally suppliedfunctions rather than internally synthesized translation machinery.

[0115] Therefore, the about 9 functional categories described previouslysimilarly can constitute an auxotrophic basic genetic operating systemof the invention. However, depending on the fundamental genes andcategories selected, the number of genes can be, for example, 151 orless. As such, an auxotrophic minimal gene set will contain at least onenon-functional gene within, for example, the constituent genes describedpreviously which are sufficient to support viability.

[0116] Exemplary fundamental genes and their gene product functionswithin each of the functional categories and subgroups are shown inFIG. 1. Orthologous genes which can similarly substitute for those shownin FIG. 1 are set forth in Table 4 below. Given the teachings andguidance provided herein those skilled in the art will know or candetermine, other orthologs or nonorthologous displacements thatsimilarly can substitute for one or more of the fundamental genes shownin FIG. 1 or Table 4. Therefore, the invention provides a basic geneticoperating system sufficient to direct autonomous auxotrophic viabilityof a host nanomachine having about 151 or less fundamental genes thatconsists of substantially the same fundamental genes show in FIG. 1,Table 4, orthologs or nonothorologous displacements thereof.

[0117] Any of the auxotrophic basic genetic operating systems describedabove, such as those directing the synthesis and maintenance of basiccellular viability functions, can be packaged into a particle envelopeto produce an autonomously viable auxotrophic nanomachine of theinvention in the presence of the corresponding auxotrophic biomolecule.Particle envelopes can include, for example, any semi-permeablepartitioning biocompatible material that maintains separation of thebasic genetic operating system or nanomachine genome, nanomachinemacromolecular structures, macromolecules and organic molecules from theexternal environment. Particle envelopes also can include otherphysical, chemical or electric forces that can generate amicroenvironment for separation of nanomachine from non-nanomachinecomponents. As with basic genetic operating systems programmed forprototrophic cellular life functions, the auxotrophic basic geneticoperating systems can be programmed similarly to direct the biosynthesisand maintenance of cellular life functions. Such cellular life functionsinclude, for example, viability, replication, transcription,translation, cell division, energy generation, cellular homeostasis,adhesion, motility, migration, environmental adaption, chemotaxis andimmune and effector cell responses. Other cellular life functions,biochemical or physiological activities or operations well known tothose skilled in the art also can be programmed separably or togetherwith the above cellular life functions.

[0118] The invention provides a basic genetic operating system for anautonomous prototrophic nanomachine having a nanomachine genome encodinga minimal gene set sufficient for autonomous prototrophic replication.The nanomachine genome can direct synthesis of the minimal gene set in arelative order of functional categories having the functions ofreplication, transcription, translation, aerobic metabolism andglycolysis, pyruvate dehyrogenase and pentose phosphate pathways,respectively. Also provided is a basic genetic operating system for aprototrophic nanomachine, further having functional categories of theminimal gene set for carbohydrate metabolism, central intermediarymetabolism, nucleotide metabolism, signal transduction regulation,transport and binding proteins, particle division, chaperone system,fatty acid/lipid metabolism, particle envelope and housekeepingfunctions.

[0119] The invention also provides a basic genetic operating system foran autonomous auxotrophic nanomachine having a nanomachine genomeencoding a minimal gene set sufficient for autonomous replication in thepresence of an auxotrophic biological molecule. The nanomachine genomecan direct synthesis of the minimal gene set in a relative order offunctional categories having the functions of replication,transcription, translation, aerobic metabolism and glycolysis, pyruvatedehydrogenase, and pentose phosphate pathways, respectively. Furtherprovided is a basic genetic operating system for an auxotrophicnanomachine further having functional categories of the minimal gene setfor carbohydrate metabolism, central intermediary metabolism, nucleotidemetabolism, signal transduction regulation, transport and bindingproteins, particle division, chaperone system, fatty acid/lipidmetabolism, particle envelope and housekeeping functions.

[0120] A basic genetic operating system of the invention specifying thegenetic programming for replication competent nanomachines is a nucleicacid, or a functional equivalent of a nucleic acid, that can serve as agenome for a biosynthetic cell or nanomachine. Encoded within a basicgenetic operating system sufficient for replication competence are, forexample, the required gene products that are obligatory to synthesizeand sustain foundational functions of the constituent components andprocesses of this cellular life function. Whether a basic geneticoperating system provides the genetic information for any of variousnon-replicative nanomachines or for any of various replication competentnanomachines, a basic genetic operating system differs from a completegenome, for example, because it duplicates or more closely approximatesa genetic copy of genes, or functional fragments thereof, that areessential for the engineered replicative or non-replicative cellularlife function. Therefore, a basic genetic operating system is a simplerand more efficient genome compared to naturally occurring genomesbecause it lacks unnecessary or redundant genetic information orstructure.

[0121] As a streamlined copy of genes that are obligatory to sustain,for example, replication competence, a basic genetic operating systemconstitutes a minimal compilation of genes that are required for thebiosynthesis and maintenance of this cellular life function. Aprototrophic basic genetic operating system will encode a completeminimal gene set whereas an auxotrophic basic genetic operating systemwill encode, for example, at least one non-functional gene within aminimal gene set whose function can be supplied by exogenoussupplementation. Therefore, a basic genetic operating system specifyingautonomous replication can, by itself, substitute for, or function as, acellular or nanomachine genome sufficient to support autonomousreplication for at least one cycle of replication. Additionally, and asdescribed further below, a basic genetic operating system also can becombined with other genes and gene sets to augment the geneticinstructions of the basic operating system. Inclusive of other genes,can, for example, enable a host nanomachine to perform and maintain awide variety of biochemical activities and operations in conjunctionwith those constituting fundamental cellular life functions such asreplication.

[0122] A minimal gene set sufficient to support either prototrophic orauxotrophic replication competence includes, for example, genes thatfall within a number of functional categories. In a simple form, areplication competent minimal gene set will include, for example, aminimal gene set sufficient for viability and fundamental genessufficient for replication of the genome. Where a genome is DNA suchgenes can include, for example, DNA polymerase and related elementaryreplication factors. In comparison, where a genome is RNA, such genescan include, the requisite reverse transcriptase or RNA polymeraserequired for the engineered replication mechanism.

[0123] More complex replication competent minimal gene sets, canadditionally include, for example, fundamental genes required fornanomachine particle division and membrane biogenesis. In the absence offundamental functions for particle division, a replication competenthost nanomachine can replicate its genome but not substantially divideinto daughter particles. A basic genetic operating system specifyingfundamental functions for replication in the absence of particledivision functions can result in production of a particle having, forexample, two or more genomes in its intraparticle space. Inclusion ofmembrane biogenesis functions, such as fatty acid and phospholipidmetabolism, in such a replication competent basic genetic operatingsystem can allow a host nanomachine to expand in size and volume toaccommodate the additional nucleic acid mass. Inclusion of fundamentalgenes sufficient for particle division or membrane biogenesis willresult in protrotrophic basic genetic operating systems for thesereferenced activities.

[0124] Alternatively, such host nanomachines can be engineered andmaintained as auxotrophs for the above fundamental functions of membranebiogenesis, particle division or both. Gene products or even nucleicacids encoding these functions which are, for example, separable fromthe basic genetic operating system can be introduced into thenanomachine to allow particle enlargement or induce particle division.

[0125] Although described with reference to membrane biogenesis andparticle division in connection with replication competent nanomachines,such strategies and modes of operation are equally applicable for bothnon-replicative and replication competent nanomachine species as well asfor a single auxotrophic fundamental gene, two or more auxotrophicfundamental genes, basic genetic operating systems engineered to beauxotrophic for pathways and networks. Given the teachings and guidanceprovided herein, those skilled in the art will know, or can routinelydetermine, various different combinations and permutations forprototrophic and auxotrophic basic genetic operating systems, theirrespective requirements for operation and modes of rescuing anauxotrophic phenotype.

[0126] Additionally, fundamental genes encoding augmentory rudimentaryfunctions also can be included in a basic genetic operating systemcontaining a minimal gene set sufficient for replication competence.Such augmentory rudimentary functions can include, for example,fundamental genes encoding polypeptide turnover and folding; purine,pyrimidine, nucleoside and nucleotide biosynthesis; chaperones, andregulatory functions. For example, the additional M. gennitalium genesset forth in FIG. 2 compared to FIG. 1, and the exemplary orthologsshown in Table 4 are examples of a fundamental genes that can becontained in a minimal gene set sufficient for replication compared toone encoding gene products sufficient for viability. Other examples ofminimal gene sets that support autonomous host replication are describedin, for example, in Mushegian and Koonin, supra; Koonin et al., supra;Hutchison et al., supra, and at NCBI URLncbi.nlm.nih.gov/cgi-bin/Complete_Genomes/mglist, supra. The constituentgenes and gene products and their interrelationships or independencewith respect to other functional categories and cellular life functionsis described further below.

[0127] Functional categories of genes within a minimal gene setconstituting the genetic programming sufficient to support replicationas a cellular life function include, for example, about fifteen or lessfundamental biochemical processes. Nine of these functional categoriesinclude those described above for a minimal gene set sufficient forviability. Similarly, the fifteen or less functional categories alsofall under the general groupings of biosynthetic, metabolic andhomoeostatic processes. The biosynthetic groupings include, for example,the functional categories of replication, transcription, translation andparticle envelope production.

[0128] Metabolic processes include, for example, energy metabolism,carbohydrate metabolism, central intermediary metabolism, nucleotidemetabolism and fatty acid and phospholipid metabolism. Energy metabolismcan further include the functional categories of aerobic metabolism andanaerobic metabolism. Glycolysis, pyruvate dehydrogenase and the pentosephosphate pathways are specific biochemical pathways supplying high freeenergy molecules such as ATP, NADH and NADPH under aerobic conditions.Any of these energy metabolism subgroups of fundamental genes aresufficient to supply adequate energy supplies for autonomousnanomachines programmed by replication competent or non-replicativebasic genetic operating systems. Carbohydrate metabolism includes, forexample, fundamental genes active in sugar conversion. Nucleotidemetabolism includes, for example, de novo or salvage pathway synthesisof purine and pyrimidine bases, nucleosides and nucleotides.

[0129] Function categories within the homoeostatic processes include,for example, regulatory functions, transport and binding functions,particle division, chaperone functions and housekeeping functions.

[0130] Those skilled in the art will know what fundamental genes are, orcan be, contained within each category, including for example, thosederived from procarvotic and eucaryotic sources. Exemplary listings offunctional categories and constituent minimal gene set sufficient for abasic genetic operating system to direct a replication competentautonomous nanomachine is shown in FIG. 2 and Table 4. Therefore, thefunctional categories constituting a minimal gene set sufficient for acellular life function such as replication competence can be derivedfrom a single species or multiple species. Similarly, fundamental genesdetermine to fall within a functional category also will include, forexample, functional equivalents such as orthologs and nonorthologousdisplacements as well as functional fragments thereof.

[0131] As with non-replicative systems, various combinations andpermutations of functional categories for a basic genetic operatingsystem programmed to direct replication competent autonomousnanomachines, such as those shown in FIG. 2 and Table 4, for example,can be produced depending on the need and desired operation of the hostnanomachine. The design considerations and engineering ofnon-replication competent basic genetic operating systems tailored for aparticular nanomachine application are also directly applicable toreplication competent basic genetic operating systems. For example, areplication competent nanomachine can be programmed to function undercompletely aerobic conditions, or alternatively, under anaerobicconditions as described previously. Similarly, a replication competentnanomachine also can be programmed to generate macromolecules by de novoor salvage biosynthesis. Further, for example, if a nanomachine of theinvention is desired to exhibit particle-particle or particle-matrixadhesion, migration, motility, cytokine regulation, growth factorregulation, immune and effector mechanism or chemotaxis to perform atargeted application, then these functional categories and theirconstituent fundamental genes can be included within a replicationcompetent basic genetic operating system of the invention.

[0132] Numerous other combinations, substitutions and permutations offunctional categories can be made in a basic genetic operating system ofthe invention to tailor the performance of either an autonomousprototrophic or auxotrophic nanomachine to a particular application.Such other modifications of functional categories include, for example,those described previously with prototrophic and auxotrophicnon-replicative systems. Those skilled in the art will know whichfunctional categories can be combined, modified or substituted toaccomplish a predetermined activity, cellular life function orapplication. Additionally, as with the other functional categories, thegenes within a particular biosynthetic pathway are well know to thoseskilled in the art. Similarly, using the teachings and guidance providedherein, those skilled in the art will know, or can determine, whichgenes within a biochemical pathway or physiological process arefundamental genes and can be included with a minimal gene set and whichgenes are dispensable to the efficient function and operation of ananomachine programmed with a basic genetic operating system conferringreplication competence.

[0133] A minimal gene set will include, for example, genes within afunctional category that are fundamental to a biochemical process.Fundamental genes for replication competence include, for example, thosegenes that are essential to the process as well as those elementarygenes that augment the performance of a biochemical process tocomparable cellular or reference standard levels. For example, a basicgenetic operating system specifying replication competent programmingcan additionally include, for example, fundamental genes encoding denovo nucleotide biosynthesis compared to non-replicative basic systems.The inclusion of additional nucleotide metabolism functions cancompensate for the added requirement necessary to replicate thenanomachine genome. Those skilled in the art will know, or candetermine, fundamental genes that encode either an essential function oran elementary function within a minimal gene set. Similarly, whether incontext of replication competent or non-replicative basic geneticoperating systems, those skilled in the art also will understand thataugmentation of a elementary process, and therefore includable as afundamental gene, differs from optimization.

[0134] The functional categories constituting a replication competentbasic genetic operating system of the invention can be arranged inessentially any desired physical or functional order so long as allgenes of the minimal gene set are present and operative. However,arranging the functional categories in relative order of importance canaugment the efficiency of the host replication competent nanomachineoperation. Similarly, arranging the functional categories in relativeorder of importance also can increase the quality of a particularnanomachine product or activity. Depending on the desired use of anautonomous prototrophic or auxotrophic nanomachine of the invention, thefunctional gene categories can be selectively arranged to optimize orregulate, for example, the genetic programming of the basic geneticoperating system, nanomachine operation efficiency or genome size.

[0135] One arrangement of functional categories within a replicationcompetent basic genetic operating system can be, for example, in therelative order of gene product use to achieve the encoded replicationand supporting functions. To sustain cellular life functions and enablegenome replication, a host nanomachine should be able to biosynthesize,for example, component macromolecules sufficient for replication,transcription, translation and at least one pathway of energyproduction. One relative order of nanomachine use can be, for example, arelative order of fundamental genes constituting the functionalcategories of replication, transcription and translation categories,respectively, followed by functional categories specifying nanomachineenergy sources. Alternatively, fundamental genes constituting one ormore energy sources can be, for example, placed prior to or between thebiosynthetic functional categories. Such energy sources can be, forexample, fundamental gene sets sufficient for either or both aerobicmetabolism and anaerobic metabolism, or a pathway thereof.

[0136] The remainder of the functional categories of genes sufficientfor replication competence of a host nanomachine can be essentially anydesired order depending on the targeted application of nanomachine anddesired efficiency. One exemplary order of the remaining categories canbe, for example, carbohydrate metabolism, central intermediarymetabolism, nucleotide metabolism, regulatory functions such as signaltransduction, transport and binding proteins, particle division,chaperone functions, fatty acid and lipid metabolism, particle envelopegeneration and housekeeping functions, respectively. The number ofpermutations and combinations of functional category order are many.Those skilled in the art will know what order and combination offunctional categories can be made within a basic genetic operatingsystem to achieve a desired result. Therefore, the invention provides abasic genetic operating system having functional categories describedabove and set forth in FIG. 2 and Table 4 arranged in all possibleorders. Additionally, any of the fundamental genes within one or more ofthe functional categories can be separated and the resulting portionsordered within a basic genetic operating system separately from, orindependent to, each other.

[0137] As with the prototrophic and auxotrophic basic genetic operatingsystems described previously, ordering of functional categoriesspecifying replication competent basic genetic operating systems alsocan be based on several different criteria. For example, ordering can beaccomplished with reference to physical order or temporal order. Anyparticular physical order can be accomplished, for example, by placementof fundamental genes or whole functional categories with reference toone or more genomic markers and in one or more directions as describedpreviously. Also as described previously, various temporal ordering offundamental genes or functional categories can be accomplished, forexample, by activation and repression of targeted genes and gene sets ina selected order or by a combination of selected activation andrepression and physical arrangements.

[0138] The invention also provides a basic genetic operating system foran autonomous protrophic nanomachine having a nanomachine genomeencoding a minimal gene set sufficient for directing autonomousprototrophic replication, he minimal gene set being devoid of at leastone gene selected from the group consisting of MG008, MG009, MG056,MG221, MG262, MG332, MG448 or MG449, an ortholog or a nonorthologousgene displacement thereof.

[0139] Further provided is a basic genetic operating system for anautonomous auxotrophic nanomachine having a nanomachine genome encodinga minimal gene set sufficient for directing autonomous replication inthe presence of an auxotrophic biological molecule, the minimal gene setbeing devoid of at least one gene selected from the group consisting ofMG008, MG009, MG056, MG221, MG262, MG332, MG448 or MG449, an ortholog ora nonorthologous gene displacement thereof.

[0140] As described previously with reference to basic genetic operatingsystems sufficient for viability or other non-replicative cellular lifefunctions, although the above genes include conserved regions between,for example, M. genitalium and H. influenza, they also can be consideredto encompass redundant structures or functions compared to other genesfound within their respective genomes. Similarly, MG008, MG009, MG056,MG221, MG262, MG332, MG448 or MG449, orthologs or nonorthologousdisplacements thereof also can be considered, for example, to encompassredundant structures or functions compared to the compliment of genesfound in genomes of other species as well. Additionally, some of thesegenes are unnecessary for rudimentary functions and, if desired to beincluded within a replication competent basic genetic operating systemof the invention, more appropriate to be placed in an overlying geneticprogram operated from the underlying basic system.

[0141] A replication competent basic genetic operating systems devoid ofMG008, MG009, MG056, MG221, MG262, MG332, MG448 or MG449, orthologs ornonorthologous displacements thereof, should include, for example,sufficient functional categories and constituent fundamental genes todirect the synthesis and maintenance of its host nanomachine components.Therefore, replication competent basic genetic operating systems devoidof one or more of the above genes can be constructed as, for example,simple, intermediate or complex versions of the replication competentbasic genetic operating systems described previously. Similarly, anyarchitectural design or arrangement of functional categories orconstituent fundamental genes also can be engineered and constructed fora prototrophic or auxotrophic basic genetic operating system devoid ofthe above eight genes. Those skilled in the art will know, or candetermine a suitable genetic structure for a particular targetedapplication of such replication competent host nanomachines.

[0142] Also provided by the invention is a basic genetic operatingsystem for an autonomous prototropic nanomachine having a nanomachinegenome encoding a minimal gene set sufficient for directing autonomousprototrophic replication, the nanomachine genome having less than about250 kilobases (kb) in size. Further provided is a basic geneticoperating system for an autonomous auxotrophic nanomachine having ananomachine genome encoding a minimal gene set sufficient for directingautonomous auxotrophic replication in the presence of an auxotrophicbiological molecule, the nanomachine genome having less than about 250kilobases (kb) in size.

[0143] A basic genetic operating system containing a minimal gene setsufficient for viability can be constructed to be any size so long as itcan be packaged into a particle envelope or other partitioningstructure. Precise structures can be designed and synthesized, forexample, to conserve or reduce space, partially or maximally miniaturizethe genome linear or condensed size, increase structural or functionalefficiency, optimize expression or regulatory element usage or tailoredto include only relevant functional domains.

[0144] Those skilled in the art will know, or can readily design, a widerange of sizes for a basic genetic operating system sufficient to conferreplication competence, given the teachings and guidance providedherein. For example, a minimal gene set such as that shown in FIG. 2 orcorresponding orthologous genes shown in Table 4 which are sufficient tospecify replication competence can be organized into a basic geneticoperating system of about 250 kilobase (kb) pairs or less. For example,juxtaposition of intronless versions of all shown fundamental genes canresult in a nucleic acid of about 248,124 bp. Such a minimal gene setencodes about 247 fundamental genes for a total of about 82,708 aminoacids.

[0145] Inclusion of naturally occurring expression and regulatoryelements, heterologous elements or combinations thereof, operationallylinked to the intronless genes can be accomplished with minimal increasein nucleic acid size. All of the considerations and possible alternativeengineering designs described previously in reference to non-replicativeversions also are directly applicable for basic genetic operatingsystems programming replication competence. One additional considerationbeing, however, that the replication competent basic genetic operatingsystem contain at least indispensable fundamental genes within thereplication functional category.

[0146] Therefore, a basic genetic operating system of the inventionprogramming nanomachine cellular life functions that are replicationcompetent can be substantially smaller than about 250 kb. For example, abasic genetic operating system sufficient for replication competence canbe about 240 kb or less, 230 kb or less, 220 kb or less, 210 kb or less,and even about 200 kb or less. It is also possible to reduce in half thesize of such basic genetic operating systems to about 125 kb by, forexample, substantial overlap and truncation of fundamental genes thatconstituting a minimal gene set. Other architectural designs well knownto those skilled in the art similarly can be used to condense oroptimize the structure of a basic genetic operating system of theinvention.

[0147] As with the non-replicative basic genetic operating systemsdescribed previously, a replication competent basic genetic operatingsystems of the invention also can include, for example, variousstructural features that facilitate the transfer of information intoencoded polypeptides and the operation of cellular life functions of ananomachine. Additionally, the basic genetic operating systems of theinvention can be designed as double stranded or single stranded genomicstructures. The number of constituent genes within a functional categorycan vary, for example, depending on the targeted application of the hostnanomachine. Considerations for which constituent fundamental genes toinclude have been described previously and include, for example, whetherthe programming is engineered for de novo or salvage biosyntheticactivities, replication within an intracellular or extracellularphysiological environment or an extracellular non-physiologicalenvironment or whether the basic genetic operating system specifiesprototrophic or auxotrophic nanomachine autonomy.

[0148] Generally, fundamental genes sufficient to support autonomousprototrophic replication can be grouped, for example, into about 24genes in a replication gene category, about 14 genes in a transcriptiongene category, about 94 genes in a translation gene category, about 13genes in an aerobic metabolism gene category, about 16 genes in an agene category, constituting glycolysis, pyruvate dehydrogenase andpentose phosphate pathways, about 3 genes in a carbohydrate metabolismgene category, about 13 genes in a central intermediary metabolism genecategory, about 18 genes in a nucleotide metabolism gene category, about4 genes in a signal transduction regulation gene category, about 23genes in a transport/binding protein gene category, about 4 genes in aparticle division gene category, about 11 genes in a chaperone systemgene category, about 3 genes in a fatty acid/lipid metabolism genecategory, about 3 genes in a particle envelope gene category, and about4 genes in a housekeeping function gene category. Fundamental genessufficient to support autonomous auxotrophic replication can contain,for example, at least one non-functional fundamental gene within one ormore of these categories. Therefore, a basic genetic operating systemfor an autonomous auxotrophic nanomachine encodes a minimal gene setsufficient for autonomous replication in the presence of an auxotrophicbiological molecule which contains, for example, about 246 or lessfundamental genes.

[0149] The functional category containing fundamental genes functioningin replication processes include, for example, a DNA polymerase encodinggene, helicase, topoisomerase, and recombination and repair enzymes.Exemplary fundamental genes for replication are shown in FIG. 2. Thetranscription functional category contains RNA polymerase, basictranscription factors, nucleases and modifying enzymes, for example. Thecategory containing fundamental genes functioning in the translationprocesses can be further divided, for example, into four furthersubgroups. These translation subgroups can consist, for example, ofabout 25 genes that encode tRNA synthesis and modification activitiesand amino acid metabolism; about 4 genes that encode degradation andpolypeptide folding activities; about 13 genes whose gene productsfunction in polypeptide modification and translation factors, and about52 genes whose gene products function in ribosome biosynthesis, assemblyand modification. There are about 10 fundamental genes encodingglycolytic functions, about 2 fundamental genes encoding pyruvatedehydrogenase pathway gene products and about 4 fundamental genesencoding gene products that function in the pentose phosphate pathway.Specific examples of constituent fundamental genes within the variousfunctional categories sufficient for replication competence are shown inFIG. 2 and in Table 4.

[0150] Exemplary fundamental genes and their gene product functionswithin each of the above functional categories and subgroups within aminimal gene set sufficient for autonomous prototrophic and auxotrophicreplication are shown in FIG. 2. Orthologous genes which can similarlysubstitute for those shown in FIG. 2 are set forth in Table 4 below.Given the teachings and guidance provided herein those skilled in theart will know or can determine, by for example, comparative genomics andgene product function, other orthologs or nonorthologous displacementsthat similarly can substitute for one or more of the fundamental genesshown in FIG. 2 or Table 4.

[0151] Therefore, the invention provides a basic genetic operatingsystem sufficient to direct autonomous prototrophic replication of ahost nanomachine having about 247 or less fundamental genes thatconsists of substantially the same fundamental genes show in FIG. 2 orTable 4, including orthologs or nonothorologous displacements thereof. Abasic genetic operating system sufficient to direct autonomousauxotrophic replication in the presence of an auxotrophic biomoleculealso is provided which has about 246 or less fundamental genes thatconsists of substantially the same fundamental genes show in FIG. 2 orTable 4, including orthologs or nonorthologous displacements thereof.

[0152] As described previously, any basic genetic operating system ofthe invention can additionally operationally incorporate overlyinggenetic programming to a impart predetermined activity or activitiesonto a host nanomachine of the invention. Nanomachines of the inventioncan be genetically programmed to perform and carry out a wide range ofbiochemically activities or operations by constructing a nanomachinegenome that contains in addition to a basic genetic operating systempredetermined genes encoding gene products having one or more activitieswhich can execute the biochemical activity or operation.

[0153] As described previously in reference to non-replicative basicgenetic operating systems, one particular application of a prototrophicor auxotrophic replication competent basic genetic operating system isthe designed incorporation of biomolecule expression and production. Oneor more expression cassettes can be, for example, engineered into abasic genetic operating system of the invention for modular insertion ofone or more genes encoding any desired biomolecule or biomolecules,biochemical pathway or network. Expression of such biomolecules can beaccomplished by any method well known to those skilled in the artincluding, for example, constitutive or regulated. Therefore,biosynthetic regulation also can be tailored to a particular replicationcompetent nanomachine application or operation.

[0154] Biomolecules include, for example, a therapeutic macromoleculesuch,as a polypeptide, a polypeptide complex, a ribo- (RNA) ordeoxyribonucleic acid (DNA), lipid or sugar, as well as biosynthesizableorganic compounds. Biomolecules also can be produced for diagnostic orindustrial purposes. Other exemplary biomolecules have been describedpreviously.

[0155] The invention additionally provides an autonomous prototrophicnanomachine having a basic genetic operating system for autonomousprototrophic replication and a particle envelope. An autonomousauxotrophic nanomachine having a basic genetic operating system forautonomous replication in the presence of an auxotrophic biologicalmolecule and a particle envelope is also provided.

[0156] As with the non-replicative forms, any of the replicationcompetent basic genetic operating systems described above can bepackaged into a particle envelope to produce an autonomous replicationcompetent prototrophic or auxotrophic nanomachine of the invention.Auxotrophic nanomachines will function autonomously in the presence ofan auxotrophic biomolecule that compliments the non-functional gene. Asdescribed previously, particle envelopes can include, for example, anysemi-permeable partitioning biocompatible material that maintainsseparation, for example, of the basic genetic operating system,nanomachine macromolecular structures, macromolecules and organicmolecules from the external environment. A particle envelope also canallow, for example, by processes well known to those skilled in the art,the influx of nutrients, minerals and other molecules needed for theproper functioning and operation of the nanomachine as well as for theefflux of metabolic by-products and waste products.

[0157] Various biocompatible materials well known to those skilled inthe art can be used as a particle envelope. For example, a particleenvelope can be a lipid vesicle, a lipid bilayer or constructed fromsynthetic or naturally occurring materials well known to those skilledin the art and as described previously. Further, combinations of naturaland synthetic biocompatible materials also can he used for nanomachineparticle envelopes of the invention. The particle envelope also can besynthesized from genes encoded by a basic genetic operating system andtherefore self-produced. The use of lipid based membranes can performboth the functions of partitioning nanomachine components and serving asa particle envelope that can be homoeostatic regulated by inclusion offundamental genes for fatty acid and lipid metabolism, for example.Additional fundamental genes encoding membrane components functions alsocan be included in a basic genetic operating system to augment envelopeproduction or homoeostatic regulation.

[0158] Accordingly, a replication competent basic genetic operatingsystem of the invention can be programmed by inclusion, for example, ofgenes encoding for fatty acid and lipid biosynthesis to autonomouslyproduce bilayer lipid membranes similar to naturally occurring cells.Alternatively, a particle envelope can be partially or completelycomposed of non-biosynthesizable components. Particle envelopecomponents that can be biosynthetically produced can be programmed intothe nanomachine's basic genetic operating system. Non-biosyntheticallyproduced particle components can be added, for example, at formation ofthe particle envelope as well as added later to supplement the envelopecomposition or produce desirable changed in the envelope composition.

[0159] Those skilled in the art will known that replication competenceand particle division are separable for both prototrophic andauxotrophic nanomachines. For example, a nanomachine of the inventionthat is capable of autonomously duplicating its genome is a replicationcompetent nanomachine. In the absence of particle division, areplication competent nanomachine can accumulate multiple copies of itsgenome. Therefore, replication competence does not require particledivision. One advantage of replication competent, non-dividingnanomachines is that they increase expression levels of encoded genes byincreasing genomic copy number. A useful application of a replicationcompetent, non-dividing nanomachine can be, for example, for theexpression of a biomolecule because each round of autonomous replicationcan increase the copy number of the biomolecule encoded gene and itscorresponding rate of synthesis or accumulation. Inclusion offundamental genes in a basic genetic operating system sufficient toprogram particle division can additionally confer onto a hostnanomachine the ability to multiple in particle number. One advantage ofreplication competent nanomachines that also can undergo particledivision is that they are self-reproducing and therefore capable ofsustaining programmed functions over long periods of time. Thisreproduction phenotype can allow, for example, for the steady andlong-lived synthesis of a biomolecule or execution of a programmedactivity.

[0160] As described previously, initial functional operation of ananomachine can be accomplished, for example, by the inclusion ofstarter molecules and macromolecules that are sufficient to achieve atleast one round of replication, transcription or translation. Startercomponents consisting of, for example, replication, transcription ortranslation machinery, precursors or energy sources can be packagedwithin the nanomachine particle envelope in sufficient amounts to allowgenome-directed synthesis and production of threshold amounts ofnanomachine components. Autonomous programmed functions will take overto replenish fundamental components and maintain prototrophic orauxotrophic homeostasis of a nanomachine of the invention. Startercomponents can be, or obtained from, for example, cell lysates, cellularfractions, recombinant production, biochemically purification,cellular-nanomachine fusions and other sources and methods well known tothose skilled in the art and as described previously.

[0161] The nanomachines of the invention can be used in a wide varietyof therapeutic, diagnostic and industrial applications. An exemplary andnon-exhaustive list of such applications includes, for example, the useof nanomachines as a bioreactor,; for bioremediation; for the productionof a therapeutic biomolecule or as a therapeutic reagent; for theproduction of a diagnostic indicator or as a diagnostic reagent; as adelivery system; as an artificial tissues or organ system; as an energyconversion system; as a processing system; as an anabolic or catabolicsystem; for the production of biological films or coatings that mayrespond to the environment, and for cosmetic applications, includingcosmeceuticals. Nanomachines of the invention can be employed in suchapplications in a variety settings including, for example, in vivo, insitu or in vitro settings. Depending on the targeted application, suchnanomachine applications can be performed with any of the nanomachinesdescribed previously. Therefore, autonomous prototrophic or auxotrophicnon-replicative nanomachines or autonomous prototrophic or auxotrophicreplication competent nanomachines can be employed in, for example, theabove applications to produce the programmed result. Similarly, any ofsuch autonomous viable or replication competent nanomachines also can beemployed in a wide variety of other applications well known to thoseskilled in the art given the teachings and guidance provided herein.

[0162] Briefly, nanomachines can be employed as bioreactors to perform awide variety of biochemical reactions that are useful for production ofcompounds and for the treatment of solutions or materials. For example,nanomachines of the invention can be programmed and used infermentation, for the production of ethanol, for example. Methods andsubstrates for fermentation are well known in the art. Esterification,methylation and numerous other chemical modifications and processes alsocan be performed using a nanomachine of the invention as a bioreactor.Given the teachings and guidance provided herein, these and otherbioreactor methods well known in the art can be employed using as asubstitute for procaryotic or eucaryotic organisms utilized in suchmethods a nanomachine of the invention.

[0163] Additionally, any of the nanomachines of the invention also canbe employed in a bioreactor process for the production of a biomoleculeof interest. For example, and as described previously, a nanomachine canbe programmed to express from one to many different polypeptides,pathways or networks. Overexpression and regulated expression also canbe accomplished as described previously to achieve, for example, adesired production of a target polypeptide or polypeptides. Therefore,the level of encoded biomolecule, expression or programmed synthesisfrom a nanomachine can be modulated depending on the need and targetedapplication. The biomoleucle of interest can be, for example, atherapeutic polypeptide or polypeptides, a diagnostic polypeptide orother biosynthesizable indicator; or An organic compound. For example,whole or partial biochemical pathways can be expressed by a nanomachineof the invention. The gene products synthesized therefrom can carry outthe biosynthesis of various different molecules such as those describedpreviously. Other examples include incorporation of pathways for thesynthesis of polyketides, isoprenoids, glycosides, nitrogen fixation,sulfide oxidation, carbon fixation, pesticides, such as pyrrolnitrin, aswell as for various physiological responses such as antigen presentationsystem that can be used in high throughput screens (HTS) screens.

[0164] Bioremediation is another useful application of the nanomachinesof the invention. For example, the nanomachines can be programmed toperform a wide variety of environmental and industrial remediationactivities. Environmental bioremediation activities can include, forexample, the treatment of pollutants or waste, such as in an oil spillor contaminated groundwater by the use of a nanomachine programmed tobreak down the undesirable substances within the contaminant. Similarly,undesirable substances produced, or contained in, an industrial process,including food processing, is an exemplary industrial bioremediationactivity for the nanomachines of the invention. A wide variety of otherbioremediation activities well known to those skilled in the art aresimilarly applicable for use with the nanomachines of the inventions.Briefly, to substitute a nanomachine for a microorganism in abioremediation process, one skilled in the art can incorporate theactive genetic components that carry out the remediation process into abasic genetic operating system of a nanomachine. Once the genome hasbeen tailored to a particular bioremediation activity, the nanomachinecan be employed in the activity in substantially the same proportions asthe original microorganism.

[0165] Any of the nanomachines described previously also can be directlyor indirectly used for therapeutic applications. Such therapeuticapplications can include, for example, expression of a therapeuticmolecule at a defined location within an individual and delivery ofmacromolecules or organic compounds to a defined location within anindividual. Nanomachines of the invention also can be used in celltherapy-like applications, for example, where a nanomachine functionallysubstitutes for a normal cell type or generates a transient or prolongedsupply a deficient product. Nanomachines further can be employed tosupply a new cellular or molecular activity or operation to anindividual that reduces the severity of a pathological condition. All ofsuch therapeutic methods as well as others well known to those skilledin the art are applicable uses for the nanomachines of the invention.

[0166] When employed as a delivery system of therapeutic molecules,diagnostic indicators, organic compounds, and various physiological orindustrial functions, nanomachines can be programmed, for example, toconstitutively produce or regulate the production of the targetbiomolecule, activity or operation. Such methods of expression have beendescribed previously and are well known to those skilled in the art,including therapeutic, diagnostic or industrial fields.

[0167] Artificial tissues or organs can be synthesized by nanomachinesof the invention and employed in numerous therapeutic applications. Thenanomachine biosynthesis of such structures can be performed forexample, in vivo, in situ or in vitro. For example, nanomachines can beprogrammed to synthesize, secrete and self-assemble extracelluar matrixpolypeptides and other components which can be deposited within a tissueor on a biocompatable substrate. Such structures can be used directly orcombined with other components such as growth factors to augment thefunction of the artificial tissue. The nanomachine produced tissues canbe used directly by, for example, production at a targeted site orindirectly by production and transplantation into a targeted site.Similarly, organs such as blood vessels, bone marrow, and liver cellfunctions can be replicated using nanomachines as a basic cellularbuilding block of these and other tissues. Such tissues can be, forexample, produced at the desired site of tissue replacement, repair orsupplementation or ex vivo and then transplanted into a recipientindividual.

[0168] Nanomachines also can be used, for example, as a device togenerate, store or convert energy or matter. For example, differentforms of energy can be captured or harnessed through known biochemicalor physiochemical or pathways and mechanisms. A basic genetic operatingsystem can be programmed to include one or more pathways which cancapture, for example, chemical energy or mechanical energy. Nanomachinepathways and components can convert these sources of energy into, forexample, high energy molecules for storage, use or subsequent conversioninto another energy type. High energy molecules can include, forexample, ATP, NAD, NADPH, FAD, and other high energy bond containingmolecules. Such molecules can be, for example, converted into othertypes of matter, used to produce work, or converted into chemicalenergy, radiant energy such as light or heat, or converted intomechanical energy. Therefore, a nanomachine can be programmed tofunction equivocally as a cell.

[0169] Useful biosynthesizable films and coatings can additionally beproduced by any of the nanomachines of the invention described herein.Such films or coatings can be, for example, responsive to environmentalchanges.

[0170] Nanomachines can be further utilized in a wide variety ofcosmetic and reconstructive applications. Such cosmetic applications canrange from cosmetic or reconstructive surgical uses to exteriorbeautifying uses. For example, nanomachines of the invention can beemployed in reconstructive surgery as supporting biocompatiblestructures. They can be seeded or grown into a variety of differentstructures either de novo, for example, or in conjunction of a naturalor biocompatible supporting architecture. Such reconstructive prosthesescan then be implanted in an individual using various methods well knownto those skilled in the art. Cosmetic surgical applications include, forexample, any of a variety of implants for augmentation of lips, cheeks,breasts and other anatomical body areas. As beautifying cosmetics orcosmeceuticals, nanomachines of the invention can be engineered tochange physical attributes in response to various environmental stimuli.Such stimuli can include, for example, pH, osmolality, temperature andhumidity. Attributes that can be modulated in response to such stimulican include, for example, color, size and odor. Cosmeceuticals cantherefore be constructed and used as temporary or permanent cosmeticaccessories.

[0171] For any of the applications described herein, the use of ananomachine of the invention will be substantially similar to methodswell known to those skilled in the art which employ cells or cellularsystems for the same or similar application. Such cells and cellularsystems can include, for example, procaryotic cells, simple eucaryoticcells and complex eucaryotic cells. To substitute for a cell or cellularsystem, a nanomachine of the invention will contain a basic geneticoperating system sufficient to support comparable non-replicative orreplicative cellular life functions and, if necessary, additionalgenetic instructions to carry out the comparable activity or operationexhibited by the cognate procaryotic or eucaryotic cell employed in themethod. Such a programmed nanomachine is substituted in a cellular orcellular system and treated in substantially the same manner, incomparable amounts and for comparable times as would be the treatmentfor the replaced cell, for example. Therefore, a nanomachine can beadded to a method or used in a method in an effective amount which issufficient to support a comparable programmed activity from thenanomachine as would occur in a cell or cellular system undersubstantially the same conditions.

[0172] It is understood that modifications which do not substantiallyaffect the activity of the various embodiments of this invention arealso included within the definition of the invention provided herein.Accordingly, the following examples are intended to illustrate but notlimit the present invention.

EXAMPLE I

[0173] Design and Synthesis of a Basic Genetic Operation System for aReplication Competent Nanomachine

[0174] This Example shows the design and synthesis of a basic geneticoperating system for a replication competent autonomous prototrophicnanomachine.

[0175] A replication competent nanomachine was engineered using the M.genitalium genome as the genetic source of fundamental genes. Briefly,an autonomous prototrophic basic genetic operating system encoding aminimal gene set that confers replication competence was electronicallycreated from sequence data information available in public databases.The minimal gene set was engineered to contain the 15 functionalcategories shown in FIG. 2 and in Table 4. Specifically, the functionalcategories were replication, transcription, translation, aerobicmetabolism, glycolysis/pyruvate dehydrogenase/pentose phosphatepathways, carbohydrate metabolism, central intermediary metabolism,nucleotide metabolism, signal transduction regulation, transport andbinding proteins, particle division, chaperone system, fatty acid/lipidmetabolism, particle envelope and housekeeping functions. Additionally,functional and structural genomic sequences such as an origin ofreplication were also included in the electronic design, engineering andsynthesis. These genomic sequences were similarly derived from the M.genitalium genome.

[0176] The design and computer synthesis of the replication competentbasic genetic operating system was performed by combining for eachfundamental gene a nucleotide sequence corresponding to its mRNA regionand required homologous expression elements. Fundamental genes within afunctional category, or subgroups within a functional category, werethen electronically arranged to produce a gene cassette corresponding toeach respective functional category or subgroup within the replicationcompetent basic genetic operating system. Finally, the gene cassetteswere then electronically combined, along with other required genomicsequences, to produce the final computerized version of the replicationcompetent autonomous prototrophic basic genetic operating system.

[0177] Following computer synthesis, the basic genetic operating systemis chemically synthesized. Synthesis is accomplished by firstelectronically parsing the genome sequence into smaller oligonucleotidesequences that can be more efficiently synthesized. The electronicparsing is performed for both the sense and complementary antisensestrands of the basic genetic operating system. Parsing also is performedby maintaining partial complementarity between the 5′ terminus of eitherthe sense or antisense strand and the 3′ terminus of its correspondingcomplementary sequence so that adjacent oligonucleotides can be annealedwith a complementary oligonucleotide to form an overlappingoligonucleotide assembly for both strands that span the genome. The sizeof each parsed oligonucleotide can vary, but generally, will be betweenabout 50-100 nucleotides (nt) in length with an about 50% overlapbetween complementary sense and antisense strands.

[0178] Following electronic parsing, automated synthesis of theindividual oligonucleotides using phosphoramidite oligonucleotidesynthesis chemistry is then performed. Automated assembly of theoligonucleotides into the basic genetic operating system is accomplishedby sequentially annealing and ligating partially complementaryoligonucleotides to result i n the complete physical synthesis of thereplication competent basic genetic operating system of about 266,433base pairs (bp) in length. All of the above steps are described infurther detail below.

[0179] Briefly, the selected fundamental gene sequences wereelectronically reduced from genomic sequences to their respective mRNAsequences. Alternatively, fundamental gene sequences were electronicallyreduced to a minimum coding sequence by elimination in some cases, ofsome or substantially all of a fundamental gene's 5′ or 3′ untranslatedregion sequence, retaining for example, ribosome binding sites forindividual fundamental genes or cistrons when necessary. Because M.genitalium is a procaryotic organism there was no need to include in theelectronic reduction removal of intron sequences. The resultantelectronic cDNA sequences were then further engineered to includefunctional expression elements such as promoters, enhancers,suppressors, and other cis acting transcriptional or translationalsequences. Such sequences included, for example, at least an upsteampromoter and a ribosome binding site for each gene or cistron and anynecessary transcription or translation termination signals.

[0180] All 5′ and 3′ expression elements and cis acting sequences wereobtain from M. genitalium genomic sequence. The M. genitalium expressionelements and cis acting sequences were then operationally linked bycomputer synthesis to their corresponding fundamental gene within theminimal gene set of the basic genetic operating system. Effectively,inclusion of homologous expression and regulatory sequences waselectronically performed by maintaining about 100 nts or the segmentdefined as the intragenic region between the initiation of the gene andthe end of the upstream gene in the 5′ direction. Similarly, about 100nts or the segment defined as the intragenic region between thetermination of the gene and the beginning of the downstream gene in the3′ direction was maintained in each electronic version of the gene. ntregion sequence 3′ to the translation stop codon also was maintained ineach electronic version of the gene.

[0181] Following computer synthesis of each fundamental gene asdescribed above, the constituent fundamental genes for each functionalcategory or subgroup were electronically organized into a singlecontiguous sequence or gene cassette. The contiguous sequences for eachfunctional category or subgroup correspond to SEQ ID NOS:1-18. Forexample, SEQ ID NO:1 shows the about 38,596 nt sequence encoding the 24fundamental genes within the replication functional category. The genesare ordered in a 5′ to 3′ direction as they are listed in FIG. 2. Acomplete listing of each functional category or a subgroup thereof, thesize of the gene cassette encoding the category or subgroup, the numberof included fundamental genes and the corresponding SEQ ID NO is setforth below in Table 1. Except where otherwise indicated, thearrangement of each gene within a functional category or subgroupcorresponds to a 5′ to 3′ direction in the gene order listed in FIG. 2.TABLE 1 Summary of Gene Cassettes for Functional Categories. FunctionalCategory or Length Number of SEQ ID Subgroup (nt) Genes NUMBERReplication 38,596 24 1 Transcription 22,684 14 2 Translation-Part I38,459 25 3 Translation-Part II 7,400 4 4 Translation-Part III 11,138 135 Translation-Part IV 23,272 52 6 Aerobic Metabolism 10,809 13 7Glycolysis, Pyruvate 21,247 16 8 Dehydrogenase & Pentose PhosphatePathways Carbohydrate Metabolism 3,075 3 9 Central Intermediary 11,89913 10 Metabolism Nucleotide Metabolism 15,051 18 11 Regulatory Functions4,055 4 12 Transport and Binding 31,241 23 13 Particle Division 4,750 414 Polypeptide Chaperones 13,894 11 15 Fatty Acid & 2,556 3 16Phospholipid Metabolism Particle Envelope 2,601 3 17 HousekeepingFunctions 3,706 4 18 Total 266,433 247

[0182] To produce the final genome, the above gene cassettes encodingeach functional category or subgroup was consecutively arranged in a 5′to 3′ unidirectional order starting from the origin of replication toyield a single, complete electronic representation of the basic geneticoperating system for a replication competent nanomachine. The origin ofreplication was obtained from pBR322 or from E. coli as a 232 nt regionlocated at positions 4,788,167 to 4,788,398 from Genbank Accessionnumber AE005174. This origin of replication is set forth as SEQ IDNO:19. The above described nanomachine genome can be electronicallyparsed synthesized and assembled as described further below.

[0183] The above-described nanomachine genome represented by SEQ IDNOS:1-18 can be parsed electronically using a computer algorithm andcorresponding executable program which generates two sets of overlappingoligonucleotides. For example, the oligonucleotides can be parsed usingParseoligo™, a proprietary computer program that optimizes nucleic acidsequence assembly. Optional steps in sequence assembly can includeidentifying and eliminating sequences that can give rise to hairpins,repeats or other difficult sequences. Additionally, the algorithm canfirst direct the synthesis of coding regions for each fundamental geneto correspond to a desired codon preference. For example, coding regionsfor fundamental genes specify E. coli codon usages instead of M.genitalium codons can be generated. For conversion of a fundamental genesequence to another codon preference, the algorithm utilizes apolypeptide sequence to generate a DNA sequence using a specified codontable. The algorithm for this step is can be described as follows:

[0184] For the DNA sequence GENE[ ], an array of bases, is generatedfrom the protein sequence AA[ ], an array of amino acids, using aspecified codon table. a. parameters i. N Length of protein in aminoacid residues ii. L = 3N Length of gene in DNA bases iii. Q Length ofeach component oligonucleotide iv. X = Q/2 Length of overlap betweenoligonucleotides v. W = 3N/Q Number of oligonucleotides in the F set vi.Z = 3N/Q + 1 Number of oligonucleotides in the R set vii. F[1:W] set of(+) strand oligonucleotides viii. R[L:Z] set of (−) strandoligonucleotides ix. AA[1:N] array of amino acid residues x. GENE[1:L]array of bases comprising the gene b. Obtain or design a proteinsequence AA[ ] consisting of a list of amino acid residues. c. Generatethe DNA sequence, GENE[ ], from the protein sequence, AA[ ] i. For I = 1to N ii. Translate AA[J] from codon table generating GENE[I: I + 2] iii.I = I + 3 iv. J = J + 1 v. Go to ii

[0185] With or without specifying a codon preference for coding regionsof fundamental genes, the parsing algorithm can generate a set of parsedoligonucleotides corresponding to the entire length of the sense andantisense stand of the nanomacine genome. The parsing can be performedon the entire genome, on the gene cassettes that constitute functionalcategories or on shorter fragments thereof, and will depend on thepreference of the user. When polymerase chain reaction (PCR) is employedin the assembly process, for example the parsing is performed on about10-15 kb fragments of the genome because this size is within theextension range of polymerases used in the procedure. Therefore, parsingthe nanomachine genome described above in 10 kb segments would result in27 different sets of sense and antisense oligonucleotides. These setscan be assembled using the PCR method described below and then ligatedtogether to yield the completed basic genetic operating system. Theparsing algorithm can be described as follows:

[0186] Two sets of overlapping oligonucleotides are generated from GENE[]; F[ ] covers the sense strand and R[ ] is a complementary, partiallyoverlapping set covering the antisense strand. a. Generate the F[] setof oligos i. For I = 1 to W ii. F[I] = GENE [I:I + Q − 1] iii. I = I + Qiv. Go to ii b. Generate the R set of oligos i. J = W ii. For I = 1 to Wiii. R[I] = GENE [W:W − Q] iv. J = J − Q v. Go to iii c. Result is twoset of oligos F[] and R[] of Q length d. Generate the final twofinishing oligos i. S[1] = GENE [Q/2:1] ii. S[2] = GENE [L − Q/2:L]

[0187] Following parsing into two sets of overlapping, partiallycomplementary oligonucleotides, which represent the complete basicgenetic operating system of the nanomachine, the oligonucleotides arethen synthesized. In this regard, the computer output of the parsed setof oligonucleotides for both the sense and antisense strand of thenanomachine genome can be transferred to oligonucleotide synthesizerdriver software. The synthesis of sequences of about 25 to 150 nt inlength can be manufactured and assembled using the array synthesizersystem and can be used without further purification. For example, two96-well plates containing 100 nt oligonucleotides can yield a 9600 bpfragment of a gene cassette. Therefore, synthesis of an entire basicgenetic operating system for the above replication competent nanomachinecan be performed using about 28 pairs of 96 well plates. Oncesynthesized, the individual oligonucleotides can be maintained in theoriginal plates or transferred to new multi-well format plates foroligonucleotide assembly.

[0188] Assembly can be accomplished using, for example, robotics ormicrofluidics well known in the art for manipulating large numbers ofoligonucleotide samples. Robotics and microfluidics allow synthesis andassembly to be performed rapidly and in a highly controlled manner. Suchmethods are described, for example, in WO 99/14318 and in U.S.application Ser. Nos. 60/262,693 and 09/922,221.

[0189] For example, oligonucleotide parsing from the genome sequencedesigned in the computer can be programmed for synthesis where sense andantistrands are placed in alternating wells of an array. Followingsynthesis in this format, the 12 row sequences of the gene are directedinto a pooling manifold that systematically pools three wells intoreaction vessels forming the triplex structure. Following temperaturecycling for annealing and ligation, four sets of annealed triplexoligonucleotides are pooled into 2 sets of 6 oligonucleotide products,then 1 set of 12 oligonucleotide products. Each row of the syntheticarray is associated with a similar manifold resulting in the first stageof assembly of 8 sets of assembled oligonucleotides representing 12oligonucleotides each. The second manifold pooling stage is controlledby a single manifold that pools the 8 row assemblies into a singlecomplete assembly. Passage of the oligonucleotide components through thetwo manifold assemblies (the first 8 and the second single) results inthe complete assembly of all 96 oligonucleotides from the array. Theassembly module of Genewriter can include a complete set of 7 poolingmanifolds produced using microfabrication in a single plastic block thatsits below the synthesis vessels. Various configurations of the poolingmanifold will allow assembly of 96,384 or 1536 well arrays of parsedcomponent oligonucleotides. A similar strategy can be performed wherepairs of oligonucleotides are pooled instead of triplets.

[0190] An algorithm which can be implemented in a computer program forassembly of oligonucleotides as described above can be described asfollows:

[0191] Two sets of oligonucleotides F[1:W] R[1:Z] S[1:2] Step 1 a. For I= 1 to W b. Anneal F[1], F[I + 1], R[I], place in T[I] c. Anneal F[I +2], R[I + 1], R[I + 2] T[I + 1] d. I = I + 3 e. Go to b Step 2 a. Do thefollowing until only a single reaction remains i. For I = 1 to W/3 ii.Ligate T[I], T[I + 1] iii. I = I + 2 iv. Go to ii

[0192] Described further below is the assembly of parsedoligonucleotides corresponding to the basic genetic operating systemdescribed above following array synthesis of the oligonucleotide setsusing a multi-well format. The method additionally employs polymerasechain reaction (PCR) in a two-step procedure to facilitate assembly.

[0193] Arrayed sets of parsed overlapping oligonucleotides are obtainedby robotic instruments. Each oligonucleotide consists of 50 nts with anoverlap of about 25 base pairs (bp). The oligonucleotide concentrationis from 250 nM (250 μM/ml). 50 base oligos give T_(m)s from 75 to 85degrees C., 6 to 10 od₂₆₀, 11 to 15 nanomoles, 150 to 300 μg. Resuspendin 50 to 100 μl of H₂O to make 250 nM/ml. Equal amounts of eacholigonucleotide are combined to a final concentration of 250 μM (250nM/ml) by adding 1 μl of each to give 192 μl. Addition of 8 μl dH₂Ofollows to bring the volume up to 200 μl and a final concentration of250 μM mixed oligos. The mixture is diluted 250-fold by taking 10 μl ofmixed oligos and add to 1 ml of water (1/100; 2.5 mM) followed bytransferring 1 μl of this mixture into 24 μl 1×PCR mix. The PCR reactionincludes: 10 mM TRIS-HCl, pH 9.0; 2.2 mM MgCl₂; 50 mM KCl; 0.2 mM eachdNTP, and 0.1% Triton X-100. One U TaqI polymerase is added to thereaction. The reaction is thermoycled under the following coditions forassembly: 55 cycles of (1) 94 degrees 30 s; (2) 52 degrees 30 s, and (3)72 degrees 30 s.

[0194] Following assembly amplification, 2.5 μl of the assembly mix isadded to 100 μl of PCR mix (40× dilution). Outside primers are preparedby taking 1 μl of F1 (forward primer) and 1 μl of R96 (reverse primer)at 250 μM (250 nm/ml-0.250 nmole/μl) and adding to the 100 μl PCRreaction. This mixture provides a final concentration of 2.5 μM eacholigo. Taq1 polymerase is added (1U) and the reaction is thermocycleunder the following conditions: 35 cycles (or original protocol 23cycles) for (1) 94 degrees for 30 s; (2) 50 degrees for 30 s, and (3) 72degrees for 60 s. The product is extract with phenol/chloroform,precipitate with ethanol and the pellet is resuspended in 10 μl of dH₂Oand analyze on an agarose gel.

[0195] An alternative method for assembly of parsed oligonucleotidescorresponding to the basic genetic operating system described abovefollowing array synthesis of oligonucleotide sets is provided below. Themethod assembles parsed oligonucleotides using a Taq1 ligationprocedure.

[0196] Briefly, arrayed sets of parsed overlapping oligonucleotides ofabout 25 to 150 bases in length each, with an overlap of about 12 to 75base pairs (bp), are obtained. The oligonucleotide concentration is from250 nM (250 μM/ml). For example, 50 base oligos give T_(m)s from 75 to85 degrees C., 6 to 10 od₂₆₀, 11 to 15 nanomoles, 150 to 300 μg. Theoligonucleotides are resuspended in 50 to 100 ml of H₂O to make 250nM/ml.

[0197] Using a robotic workstation, for example, a Beckman Biomekautomated pipetting robot or another automated lab workstation, equalamounts of forward and reverse oligonucleotides are combined pairwise.Equal volumes (10 μl) of forward and reverse oligonucleotides are mixedin a new 96-well v-bottom plate to provide one array with sets of duplexoligonucleotides at 250 μM, according to pooling scheme Step 1 in Table2. An assembly plate is prepared by taking 2 μl of each oligomer pairand adding to a fresh plate containing 100 μl of ligation mix in eachwell. This procedure gives an effective concentration of 2.5 μM or 2.5nM/ml. From each well of these wells, 20 μl is transferred to a freshmicrowell plate and 1 μl of T4 polynucleotide kinase and 1 μl of 1 mMATP subsequently added to each well. Each reaction will have 50 pmolesof oligonucleotide and 1 nmole ATP. The reactions are incubated at 37degrees C. for 30 minutes.

[0198] Initiation of assembly is performed according to Steps 2-7 ofTable 2. For example, pooling Step 2 is performed by mixing eachsuccessive well with the next. Taq1 ligase (1 μl) is then added to eachmixed well and the mixture is cycled once at 94 degrees for 30 sec; 52degrees for 30 s; then 72 degrees for 10 minutes.

[0199] Further assembly is performed according to step 3 of Table 2 ofthe pooling scheme and cycle according to the temperature schemedescribed above. Similarly, steps 4 and 5 of the pooling scheme aresubsequently performed for further assembly and also cycled according tothe temperature scheme above. Subsequent performance of step 6 of thepooling scheme is accomplished by transferring 10 μl of each mix into afresh microwell and step 7 of the pooling scheme is accomplished bypooling the remaining three wells. The reaction volumes for each ofthese step within the pooling scheme will be: Initial plate has 20 ulper well. Step 2 20 ul + 20 ul = 40 ul Step 3  80 ul Step 4 160 ul Step5 230 ul Step 6 10 ul + 10 ul = 20 ul Step 7 20 + 20 + 20 = 60 ul finalreaction volume

[0200] A final PCR amplification is then performed by taking 2 μl offinal ligation mix and add to 20 μl of PCR mix containing 10 mMTRIS-HCl, pH 9.0, 2.2 mM MgCl₂, 50 mM KCl, 0.2 mM each dNTP and 0.1%Triton X-100.

[0201] The outside primers are prepared by taking 1 μl of F1 (forwardprimer) and 1 μl of R96 (reverse primer) at 250 μM (250 nm/ml-0.250nmole/μl) and add to the 100 μl PCR reaction giving a finalconcentration of 2.5 μM each oligo. Add 1 U Taq1 polymerase and cyclefor 35 cycles under the following conditions: 94 degrees for 30 s; 50degrees for 30 s; and 72 degrees for 60 s. The mixture is extracted withphenol/chloroform and precipitated with ethanol. The pellet is resuspendin 10 μl of dH₂O and analyze on an agarose gel. TABLE 2 Pooling schemefor ligation assembly. Ligation method - Well pooling scheme STEP FROMTO 1 All F All R 2 A1 A2 A3 A4 A5 A6 A7 A8 A9 A10 A11 A12 B1 B2 B3 B4 B5B6 B7 B8 B9 B10 B11 B12 C1 C2 C3 C4 C5 C6 C7 C8 C9 C10 C11 C12 D1 D2 D3D4 D5 D6 D7 D8 D9 D10 D11 D12 E1 E2 E3 E4 E5 E6 E7 E8 E9 E10 E11 E12 F1F2 F3 F4 F5 F6 F7 F8 F9 F10 F11 F12 G1 G2 G3 G4 G5 G6 G7 G8 G9 G10 G11G12 H1 H2 H3 H4 H5 H6 H7 H8 H9 H10 H11 H12 3 A2 A4 A6 A8 A10 A12 B2 B4B6 B8 B10 B12 C2 C4 C6 C8 C10 C12 D2 D4 D6 D8 D10 D12 E2 E4 E6 E8 E10E12 F2 F4 F6 F8 F10 F12 G2 G4 G6 G8 G10 G12 H2 H4 H6 H8 H10 H12 4 A4 A8A12 B4 B8 B12 C4 C8 C12 D4 D8 D12 E4 E8 E12 F4 F8 F12 G4 G8 G12 H4 H8H12 5 A8 B4 B12 C8 D4 D12 E8 F4 F12 G8 H4 H12 6 B4 C8 D12 F4 G8 H12 7 C8F4

[0202] Another alternative method for assembly of parsedoligonucleotides corresponding to the basic genetic operating systemdescribed above following array synthesis of oligonucleotide sets isadditionally described below. This method assembles parsedoligonucleotides using a TaqI synthesis and stepwise assembly.

[0203] Briefly, arrayed sets of parsed overlapping oligonucleotides ofabout 25 to 150 bases in length each, with an overlap of about 12 to 75base pairs (bp), are obtained as described above and resuspended in 50to 100 ml of H₂O to make 250 nM/ml. Similarly, manipulations of samplesis performed using robotics as described previously.

[0204] Two working multi-well plates containing forward and reverseoligonucleotides in a PCR mix at 2.5 mM are prepared and 1 μl of eacholigo are added to 100 μl of PCR mix in a fresh microwell providing oneplate of forward and one of reverse oligos in an array. Cycling assemblyis then initiated as follows according to the pooling scheme outlined inTable 3. In the present example, 96 cycles of assembly can beaccomplished according to this scheme.

[0205] To begin assembly, 2 μl of oligonucleotides in well F-E1 istransferred to a fresh well. Similarly, 2 μl of oligonucleotides in wellR-E1 is transferred to a fresh well and 18 μl of 1×PCR mix and 1 U ofTaq1 polymerase are added. The mixture is cycled once under thefollowing conditions: (1) 94 degrees for 30 s; (2) 52 degrees for 30 s,and (3) 72 degrees for 30 s. Subsequently, 2 μl of oligonucleotides fromwell F-E2 and from well R-D12 is transferred to the reaction vessel. Themixture is cycled once according to the temperatures conditionsdescribed above. The pooling and cycling is repeated according to thescheme outlined in Table 3 for about 96 cycles.

[0206] A PCR amplification is then performed by taking 2 μl of finalreaction mix and adding it to 20 μl of a PCR mix comprising: 10 mMTRIS-HCl, pH 9.0; 2.2 mM MgCl2; 50 mM KCl; 0.2 mM each dNTP, and 0.1%Triton X-100.

[0207] Outside primers are prepared by taking 1 μl of F1 and 1 ml of R96at 250 mM (250 nm/ml- 0.250 nmole/ml) and adding to the above 100 μl PCRreaction. This procedure yields a final concentration of 2.5 μM eacholigonucleotide. 1 U Taq1 polymerase is subsequently added and thereaction is cycled for about 23 to 35 cycles under the followingconditions: (1) 94 degrees for 30 s; (2) 50 degrees for 30 s, and (3) 72degrees for 60 s. The reaction is subsequently extracted withphenol/chloroform, precipitated with ethanol and resuspend in 10 ml ofdH20 for analysis on an agarose gel.

[0208] For initial pooling of the oligonucleotides, equal amounts offorward and reverse oligonucleotide pairs are added by taking 10 μl offorward and 10 μl of reverse oligonucleotide and mixing in a new 96-wellv-bottom plate. This procedure provides one array with sets of duplexoligonucleotides at 250 mM, according to pooling scheme Step 1 in Table3. An assembly plate is prepared by taking 2 μl of each oligomer pairand adding them to the plate containing 100 μl of ligation mix in eachwell. This gives an effective concentration of 2.5 μM or 2.5 nM/ml.About 20 μl of each well is transferred to a fresh microwell plate inaddition to 1 μl of T4 polynucleotide kinase and 1 μl of 1 mM ATP. Eachreaction will have 50 pmoles of oligonucleotide and 1 nmole ATP. Thereaction is incubated at 37 degrees for 30 minutes.

[0209] Nucleic acid assembly was initiated according to Steps 2-7 ofTable 3. For step 2, pooling is carried out by mixing each well with thenext well in succession. Specifically, 1 μl of Taq1 ligase to is addedto each mixed well and cycled once as follows: (1) 94 degrees for 30sec; (2) 52 degrees for 30 s, and (3) 72 degrees 10 minutes.

[0210] Subsequently, step 3 of pooling scheme is carried out and cycledaccording to the temperature scheme described above. In like manner,steps 4 and 5 of the pooling scheme are then carried out and cycledaccording to the temperature scheme above. Step 6 of the pooling schemeis performed by taking 10 μl of each mix into a fresh microwell. Poolingthe remaining three wells completes performance of step 7 of the poolingscheme. The reaction volumes will be (initial plate has 20 μl per well):Step 2 20 μl + 20 μl = 40 μl Step 3  80 μl Step 4 160 μl Step 5 230 μlStep 6 10 μl + 10 μl = 20 μml Step 7 20 + 20 + 20 = 60 μl final reactionvolume

[0211] Following completion of the steps described above, a final PCRamplification is performed by taking 2 μl of the final ligation mix andadding it to 20 μl of PCR mix comprising: 10 mM TRIS-HCl, pH 9.0; 2.2 mMMgCl2; 50 mM KCl; 0.2 mM each dNTP, and 0.1% Triton X-100.

[0212] Outside primers are prepared by taking 1 μl of F1 and 1 μl of R96at 250 mM (250 nm/ml-0.250 nmole/ml) and adding them to the above PCRreaction above giving a final concentration of 2.5 μM for eacholigonucleotide. Subsequentlly, 1 U of Taq1 polymerase is added andcycled for about 23 to 35 cycles under the following conditions: (1) 94degrees for 30 s; (2) 50 degrees for 30 s, and (3) 72 degrees for 60 s.The product is extracted with phenol/chloroform, precipitate withethanol, resuspend in 10 μl of dH2O and analyzed on an agarose gel.TABLE 3 Pooling scheme for assembly using Taq1 polymerase (alsotopoisomerase II). Step Forward oligo Reverse oligo 1 F E 1 + R E 1Pause 2 F E 2 + R D 12 Pause 3 F E 3 + R D 11 Pause 4 F E 4 + R D 10Pause 5 F E 5 + R D 9 Pause 6 F E 6 + R D 8 Pause 7 F E 7 + R D 7 Pause8 F E 8 + R D 6 Pause 9 F E 9 + R D 5 Pause 10 F E 10 + R D 4 Pause 11 FE 11 + R D 3 Pause 12 F E 12 + R D 2 Pause 13 F F 1 + R D 1 Pause 14 F F2 + R C 12 Pause 15 F F 3 + R C 11 Pause 16 F F 4 + R C 10 Pause 17 F F5 + R C 9 Pause 18 F F 6 + R C 8 Pause 19 F F 7 + R C 7 Pause 20 F F 8 +R C 6 Pause 21 F F 9 + R C 5 Pause 22 F F 10 + R C 4 Pause 23 F F 11 + RC 3 Pause 24 F F 12 + R C 2 Pause 25 F G 1 + R C 1 Pause 26 F G 2 + R B12 Pause 27 F G 3 + R B 11 Pause 28 F G 4 + R B 10 Pause 29 F G 5 + R B9 Pause 30 F G 6 + R B 8 Pause 31 F G 7 + R B 7 Pause 32 F G 8 + R B 6Pause 33 F G 9 + R B 5 Pause 34 F G 10 + R B 4 Pause 35 F G 11 + R B 3Pause 36 F G 12 + R B 2 Pause 37 F H 1 + R B 1 Pause 38 F H 2 + R A 12Pause 39 F H 3 + R A 11 Pause 40 F H 4 + R A 10 Pause 41 F H 5 + R A 9Pause 42 F H 6 + R A 8 Pause 43 F H 7 + R A 7 Pause 44 F H 8 + R A 6Pause 45 F H 9 + R A 5 Pause 46 F H 10 + R A 4 Pause 47 F H 11 + R A 3Pause 48 F H 12 + R A 2 Pause

[0213] Although the invention has been described with reference to thedisclosed embodiments, those skilled in the art will readily appreciatethat the specific experiments detailed are only illustrative of theinvention. It should be understood that various modifications can bemade without departing from the spirit of the invention. Accordingly,the invention is limited only by the following claims. TABLE 4ORTHOLOGOUS FUNDAMENTAL GENES EUCARYOTIC M. genitalium H. influenza E.coli (NCBI Accession Identification) Replication MG001 DNA PolymeraseIII 0410 DNA Pol III, beta chain dnaN MG003 DNA gyrase 1688 DNA gyrase,subunit B gyrB BAA33955 (Candida) MG004 DNA gyrase 0672 DNA gyrase,subunit A gyrA P30182 (Arabidopsis) MG073 Excinuclease ABC 0656Excinuclease helicase uvrB T86424 (Human) MG091 ss DNA Binding Protein1384 ssDNA binding protein ssb P32445 (Saccharomyces) MG094 ReplicativeDNA helicase 0971 Replicative helicase dnaB MG097 DNA uracil glycosylase1155 Uracil-DNA glycosylase ung DDU32866 (Dictyostelium) MG122 DNAtopoisomerase I 0768 DNA topoisomerase I topA P13099 (Saccharomyces)MG203 DNA topoisomerase IVsub 0929 DNA topoisomerase IV sub parE P41001(Plasmodium) MG204 DNA topoisomerase IVsub 0930 DNA topoisomerase IV subparC X74738 (Saccharomyces) MG206 Excinuclease ABC 1194 Excinucleasenuclease sub uvrC MG244 DNA helicase II 0069 DNA helicase rep HJBYDH(Saccharomyces) MG250 DNA primase 1654 DNA primase dnaG MG254 DNA ligase0512 DNA ligase lig MG259 FKBP-like peptidylprolyl isomerase 0961Adenyne-specific DNA methylase hemK U12141 (Saccharomyces) MG261 DNA PolIII 0155 DNA Pol III alpha subunit dnaE MG262a Formamidopyrimidine-DNA0362 Formamidopyrimidine-DNA glycosylase mutM glycosylase MG339Recombination protein 0017 Rec A recA L15229 (Arabidopsis) MG358Holliday junction DNA helicase 1445 Holliday junction DNA helicasesubunit ruvA MG359 Holliday junction DNA helicase 1444 Holliday junctionDNA helicase subunit ruvB M96757 (Plasmodium) MG379 FAD binding protein1703 FAD-utilizing enzyme gidA JU0182 (Cucumis) MG420 DNA Pol III subdnaXp CAA91237 (Schizosaccharomyces) MG421 Excinuclease ABC 1383Excinuclease ATPase sub uvrA CAC02927 (Leishmania) MG469 Chromosomalreplication inhibitor 0411 Chromosomal replication initiator ATPase dnaATranscription MG054 Transcription elongation and 0132 Transcriptionantiterminator nusG termination factor MG104 RNase 0278 ExoribonucleasevacB P37202 (Schizosaccharomyces) MG141 N-utilzation substance protein0689 Transcription factor nusA MG177 RNA pol 0219 DNA-directed RNA Polalpha subunit rpoA P07703 (Saccharomyces) MG209 Pseudouridylate synthase1539 PseudoU synthetase yceC Q09709 (Schizosaccharomyces) MG249 RNA polsigma A factor 1655 RNA pol sigma-70 factor rpoD MG278guanosine-3′,5′-bis(diphosphate) 1135 ppGpp 3′ pyrophosphohydrolase spoT3′-pyrophophohydrolase (transcriptional regulator) MG340 RNA polymerase1636 DNA-directed RNA pol beta-prime rpoC P36594 (Schizosaccharomyces)MG341 RNA polymerase 1637 DNA-directed RNA pol beta-subunit rpoB P38420(Arabidopsis) MG346 rRNA methyltransferase (SpoU family) 0182 rRNAmethylase (SpoU family) yibK MG367 Ribonuclease III 1151 RibonucleaseIII rnc XP_015448 (Human) MG425 ATP-dependent RNA helicase 1369 RNAhelicase deaD P19109 (Drosophila) MG463 rRNA (adenosine-N6,N6-)- 1671Dimethyladenosine transferase ksgA P41819 (Saccharomyces)dimethyltransferase MG465 Rnase P C5 sub 0416 RNase P protein componentrnpA Translation - Part I Amino acyl tRNA synthetases, tRNA modificationand amino acid metabolism. MG005 Ser-tRNA Synthase 1248 seryl-tRNAsynthetase serS CAB61772 (Schizosaccharomyces) MG021 Met-tRNA Synthase0683 methionine-tRNA synthetase metG P22438 (Saccharomyces) MG035His-tRNA Synthase 1495 histidine-tRNA synthetase hisS CAA94983(Saccharomyces) MG036 Asp-tRNA Synthase 1449 aspartyl-tRNA synthetaseaspS P14868 (Human) MG083 Peptidyl-tRNA Hydrolase 1521 peptidyl-tRNAhydrolase pth Q59989 (Synechocystis) MG113 Asn-tRNA Synthase 0707asparagine-tRNA synthetase asnS P38707 (Saccharomyces) MG126 Trp-tRNASynthase 0057 tryptophanyl-tRNA synthetase trpS YWBYM (Saccharomyces)MG136 Lys-tRNA Synthase 0620 lysyl-tRNA synthetase lysU P37879(Cricetulus) MG182 Pseudouridylate Synthase 1038 pseudoU synthetase ItruA P31115 (Saccharomyces) MG194 Phe-tRNA Synthase 0716phenylalanyl-tRNA synthetase alpha chain pheS AAB51175 (Human) MG195Phe-tRNA Synthase 0717 phenylalanyl-tRNA synthetase beta chain pheTMG251 Gly-tRNA Synthase thrSp P52709 (Caenorhabditis) MG253 Cys-tRNASynthase 1215 cysteinyl-tRNA synthetase cysS AAG00579 (Human) MG266Leu-tRNA Synthase 0337 leucyl-tRNA synthetase leuS P41252 (Human) MG283Pro-tRNA Synthase proSp P26639 (Human) MG292 Ala-tRNA Synthase 0231alanyl-tRNA synthetase alaS P21894 (Bombyx) MG334 Val-tRNA Synthase 0797valyl-tRNA synthetase valS BG099272 (Human) MG336 Pyridoxal-dependent0700 aminotransferase aminnotransferase MG345 Ile-tRNA Synthase 0378isoleucyl-tRNA synthetase ileS P09436 (Saccharomyces) MG365 Met-tRNASynthase 0043 methionyl-tRNA formyltransferase fmt P28037 (Rattus) MG375Thr-tRNA Synthase 0770 threonyl-tRNA synthetase thrS P04801(Saccharomyces) MG378 Arg-tRNA Synthase 0977 arginyl-tRNA synthetaseargS AAK68226 (Caenorhabditis) MG445 tRNA (guanine-N1)-Mtase 1336 tRNA(guanine-N1)-methyltransferase trmD NP_014647 (Saccharomyces) MG455Tyr-tRNA Synthase 1003 tyrosyl-tRNA synthetase tyrS Q09692(Schizosaccharomyces) MG462 Glu-tRNA Synthase 1408 glutamyl-tRNAsynthetase gltX P13188 (Saccharomyces) Translation - Part II Degradationand folding of polypeptides MG238 Trigger factor 0128 peptidyl-prolylcis-trans isomerase tig P20081 (Saccharomyces) MG239 ATP-dependentprotease 1588 ATP-dependent protease lon MG355 ATP-dependent proteasebinding sub 0276 ATP-dependent ClpB protease ATPase clpB CAB38512(Schizosaccharomyces) MG391 Aminopeptidase 1098 leucyl aminopeptidasepepA Q09735 (Schizosaccharomyces) Translation - Part III Polypeptidemodification and translation factors MG026 Elongation factor P 1457Elongation factor P efp MG089 Elongation factor G 1700 Translationelongation factor G fusA P32324 (Saccharomyces) MG106 Formylmethioninedeformylase 0042 N-formylmethionylaminoacyl-tRNA def deformylase MG142Protein synthesis initiation factor 2 0690 Translation initiation factorIF-2, GTPase infB NP_009531 (Saccharomyces) MG143 Ribosome-bindingfactor 0694 Ribosome-binding protein rbfA MG172 Methionine aminopeptidase 1114 Methionine aminopeptidase map MG173 Initiation factor 11670 Translation initiation factor IF-1 infA MG196 Translationinitiation factor IF3 0723 Initiation factor 3 infC MG258 Peptide chainrelease factor 1 0963 Peptide chain release factor 1 prfA MG282Transcription elongation factor 0734 Transcription elongation factorgreA MG433 Elongation factor 0330 Translation elongation factor Ts tsfMG435 Ribosome releasing factor 0225 Ribosome releasing factor frrNP_011903 (Saccharomyces) MG451 Elongation factor TU 0052UDP-n-acetylglucosamine tufA Q00080 (Plasmodium) pyrophosphorylaseTranslation - Part IV Ribosome synthesis & modification MG012 Ribosomalprt S6 modification 0932 Ribosomal prt S6 modification rimK MG070Ribosomal prt S2 0329 Ribosomal prt S2 rpsB MG081 Ribosomal prt L11 163950S Ribosomal prt L11 rplK P17079 (Saccharomyces) MG082 Ribosomal prt L11638 Ribosomal prt L1 rplA P96038 (Sulfolobus) MG087 Ribosomal prt S121702 30S Ribosomal prt S12 rpsL CAB97965 (Leishmania) MG088 Ribosomalprt S7 1701 30S Ribosomal prt S7 rpsG MG090 Ribosomal prt S6 1669 30SRibosomal prt S6 rpsF P15938 (Saccharomyces) MG092 Ribosomal prt S181667 30S Ribosomal prt S18 rpsR MG093 Ribosomal prt L9 1666 50SRibosomal prt L9 rplI MG150 Ribosomal prt S10 0192 30S Ribosomal prt S10rpsJ P35686 (Oryza) MG151 Ribosomal prt L3 0193 50S Ribosomal prt L3rplC P34113 (Dictyostelium) MG152 Ribosomal prt L4 0194 50S Ribosomalprt L4 rplD P12735 (Haloarcula) MG153 Ribosomal prt L23 0195 50SRibosomal prt L23 rplW S78414 (Rattus) MG154 Ribosomal prt L2 0196Ribosomal prt L22 rplB P41569 (Aedes) MG155 Ribosomal prt S19 0197Ribosomal prt S19 rpsS P39697 (Arabidopsis) MG156 Ribosomal prt L22 019850S Ribosomal prt L22 rplV MG157 Ribosomal prt S3 0199 Ribosomal prt S3rpsC P05750 (Saccharomyces) MG158 Ribosomal prt L16 0200 50S Ribosomalprt L16 rplP T38231 (Schizosaccharomyces) MG159 Ribosomal prt L29 020150S Ribosomal prt L29 rpmC P42766 (Human) MG160 Ribosomal prt S17 0202Ribosomal prt S17 rpsQ Z46260 (Saccharomyces) MG161 Ribosomal prt L140204 50S Ribosomal prt L14 rplN AAK18863 (Caenorhabditis) MG162Ribosomal prt L24 0205 50S Ribosomal prt L24 rplX MG163 Ribosomal prt L50206 50S Ribosomal prt L5 rplE NP_015194 (Saccharomyces) MG164 Ribosomalprt S14 0207 50S Ribosomal prt S14 rpsN P10633 (Saccharomyces) MG165Ribosomal prt S8 0208 30S Ribosomal prt S8 rpsH P39027 (Human) MG166Ribosomal prt L6 0209 50S Ribosomal prt L6 rplF CAA91503(Schizosaccharomyces) MG167 Ribosomal prt L18 0210 50S Ribosomal prt L18rplR MG168 Ribosomal prt S5 0211 30S Ribosomal prt S5 rpsE P05753(Saccharomyces) MG169 Ribosomal prt L15 0213 50S Ribosomal prt L15 rplOMG174 Ribosomal prt L36 0215 50S Ribosomal prt L36 rpmJ MG175 Ribosomalprt S13 0216 Ribosomal prt S13 rpsM MG176 Ribosomal prt S11 0217Ribosomal prt S11 rpsK Q08699 (Podocoryne) MG178 Ribosomal prt L17 022050S Ribosomal prt L17 rplQ P22353 (Saccharomyces) MG197 Ribosomal prtL35 0724 50S Ribosomal prt L35 rpmI MG198 Ribosomal prt L20 0725 50SRibosomal prt L20 rplT MG232 Ribosomal prt L21 0297 50S Ribosomal prtL21 rplU MG234 Ribosomal prt L27 0296 50S Ribosomal prt L27 rpmA MG252rRNA methylase 0277 rRNA methylase (SpoU family) yjfH S48881(Saccharomyces) MG257 Ribosomal prt L31 0174 50S ribosomal protein L31rpmE MG311 Ribosomal prt S4 0218 ribosomal protein S4 rpsD CAA18654(Schizosaccharomyces) MG325 Ribosomal prt L33 0367 ribosomal protein L33rpmG MG361 Ribosomal prt L10 0060 Ribosomal protein L10 rplJ MG362Ribosomal prt L7/L12 0061 Ribosomal protein L7/L12 rplL P05387 (Human)MG363 Ribosomal prt L32 1292 Ribosomal protein L32 rpmF MG363a Ribosomalprt S20 0381 30S ribosomal protein S20 rpsT MG417 Ribosomal prt S9 084730S ribosomal protein S9 rpsI CAA21965 (Candida) MG418 Ribosomal prt L130848 Ribosomal protein L13 rplM P39473 (Sulfolobus) MG424 Ribosomal prtS15 0732 Ribosomal protein S15 rpsO CAC37508 (Schizosaccharomyces) MG426Ribosomal prt L28 0368 Ribosomal protein L28 rpmB MG444 Ribosomal prtL19 1335 Ribosomal protein L19 rplS MG446 Ribosomal prt S16 1338 30Sribosomal protein S16 rpsP U33335 (Saccharomyces) MG466 Ribosomal prtL34 0415 50S ribosomal protein L34 rpmH Aerobic Metabolism MG102Thioredoxin reductase 0570 Thioredoxin trxB NP_010640 (Saccharomyces)MG124 Thioredoxin 1221 Thioredoxin trxA P38141 (Saccharomyces) MG145 FADsynthase 0379 Nucleotidyltransferase yaaC NP_010522 (Saccharomyces)MG275 NADH Oxidase lpdp P09623 (Sus) MG398 ATP Synthase epsilon chain1603 ATP synthase F1 epsilon subunit atpC MG399 ATP Synthase beta chain1604 H+-transporting ATPase beta-subunit atpD P48413 (Cyanidium) MG400ATP Synthase gamma chain 1605 ATP synthase F1 gamma subunit atpG MG401ATP Synthase alpha chain 1606 ATP synthase F1 alpha subunit atpA P48413(Cyanidium) MG402 ATP Synthase delta chain 1607 ATP synthase F1 deltasubunit atpH MG403 ATP Synthase B chain 1608 ATP synthase F0 subunit batpF MG404 ATP Synthase C chain 1609 H+-transporting ATP synthase Cchain atpE MG405 Adenosinetriphosphatase 1610 ATP synthase F0 subunit aatpB MG408 peptide methionine sulfoxide reductase msrA NP_010960(Saccharomyces) Glycolysis, Pyruvate Dehydrogenase & Pentose PhosphatePathways MG023 Fructose-bisphosphate aldolase gatY P14540(Saccharomyces) MG063 1-phoshofructokinase 1573 1-phosphofructokinasefruK P25332 (Saccharomyces) MG066 Transketolase 1 (TK 1) 0439Transketolase 2 tkt P23254 (Saccharomyces) MG069 Phosphotransferaseenzyme IIABC_(—) crr S74697 (Synechocystis) MG111 Phosphoglucoseisomerase B 0973 Glucose-6-phosphate isomerase pgi NP_009755(Saccharomyces) MG215 6-phosphofructokinase 0400 6-phosphofructokinasepfkA P16861 (Saccharomyces) MG216 Pyruvate kinase 0970 Pyruvate kinasepykA NP_014992 (Saccharomyces) MG271 Dihydrolipoamide Dehydrogenase 0640Dihydrolipamide dehydrogenase lpd P09624 (Saccharomyces) MG272Dihydrolipoamide acetyltransferase 0641 Dihydrolipoamideacetyltransferase E2 aceF P10515 (Human) component MG273 PyruvateDehydrogenase E-1beta sub U09137 (Arabidopsis) MG274 PyruvateDehydrogenase E-1alpha sub NP_000047 (Human) MG300 Phosphoglyceratekinase 1647 Phosphoglycerate kinase pgk Q27685 (Leishmania) MG301Glyceraldehyde 3-phosphate 1138 Glyceraldehyde 3-phosphate gapA P00359(Saccharomyces) dehydrogenase dehydrogenase MG407 Enolase 0348 Enolaseeno U09194 (Mesembryanthemum) MG430 Phosphoglycerate mutase yibONP_013374 (Saccharomyces) MG431 Triosephosphate isomerase 0096Triosephosphate isomerase tpiA Q07412 (Plasmodium) CarbohydrateMetabolism MG050 deoxyribose-phosphate aldolase 0528Deoxyribose-phosphate aldolase deoC AAK68302 (Caenorhabditis) MG053phosphomannomutase 0740 Phosphomannomutase yhbF NP_014005(Saccharomyces) MG112 D-ribose-5-phosphate 3 epimerase 1370 Lytictransglycosylase yfhD NP_012414 (Saccharomyces) Central IntermediaryMetabolism MG013 5,10-methylene-tetrahydrofolate 00275,10-methylene-tetrahydrofolate folD Q04448 (Drosophila) dehydrogenasedehydrogenase MG038 Glycerol kinase 0108 Glycerol kinase glpK S36175(Human) MG047 S-adenosylmethionine synthetase 0584 S-adenosylmethioninesynthetase II metX NP_013281 (Saccharomyces) MG222 SAM-dependentmethyltransferase 0542 SAM-dependent methyltransferase yabC MG228Dihydrofolate reductase 0316 Dihydrofolate reductase folA U03885(Paramecium) MG245 5,10-methenyltetrahydrofolate synthase 02755-formyltetrahydrofolate cyclo-ligase ygfA P11586 (Human) MG293Glcerophospphoryl diester 0106 Glcerophospphoryl diester glpQphosphodiesterase phosphodiesterase MG299 Phosphotransacetylase 0612Phosphotransacetylase ptap P38503 (Methanosarcina) MG347 SAM-dependentmethyltransferase 1469 SAM-dependent methyltransferase yggH MG351Inorganic pyrophosphatase 1555 Inorganic Pyrophosphatase Ppap/ppa P28239(Saccharomyces) MG357 Acetate kinase 0613 Acetate kinase ackA MG380SAM-dependent methyltransferase 1611 Glucose-inhibited division protein,gidB P38892 (Saccharomyces) methyltransferase MG394 Serinehydroxymethyltransferase (folate 0306 Serine hydroxymethyltransferaseglyA P37291 (Saccharomyces) cycle) Nucleotide Metabolism: Purines,Pyrimidines, Nucleosides, and Nucleotides MG006 Thymidylate kinase 1582Pyrimidine kinase ycfG AAC73211 (Human) MG030 UracilPhophoribosyltransferase 0637 Uracil phosphoribosyl transferase uppU10246 (Toxoplasma) MG049 Purine-nucleoside phophorylase 1640Purine-nucleoside phophorylase deoD BC003788 (Mus) MG052 Cytidinedeaminase 0753 Cytidine deaminase Cddp/cdd P32320 (Human) MG058Phophoribosylpyrophosphate Synthase 1002 Ribose-phosphatepyrophosphokinase prsA P38689 (Saccharomyces) MG107 5′-guanylate kinase1137 Guanylate kinase gmk KIBYGU (Saccharomyces) MG118 UDP-glucose4-epimerase 1480 UDP-glucose 4-epimerase galE P04397 (Saccharomyces)MG171 Adenylate kinase 1478 Adenylate kinase adk P26364 (Saccharomyces)MG227 Thymidylate Synthase 0321 Thymidylate Synthase thyA U03885(Paramecium) MG229 Ribonucleotide Reductase 2 1054Ribonucleoside-diphosphate reductase, nrdB P42170 (Caenorhabditis) betachain MG231 Ribonucleoside-diphosphate Reductase 1053Ribonucleoside-diphosphate reductase nrdA CAB72517 (Campylobacter) MG268Deoxyguano-deoxyadeno kinase (I) sub 2 MG276 AdeninePhophoribosyltransferase 0639 Adenine phosphoribosyltransferase aptTAU22442 (Triticum) MG330 Cytidylate kinase 0628 Cytidylate kinase cmkU10120 (Mus) MG382 Uridine kinase 1266 Uridine kinase udk L31784 (Mus)MG434 uridylate kinase 0479 Uridine 5′-monophosphate kinase pyrH P37142(Daucuc) MG453 UDP-glucose pyrophosphorylase 0229 Glucosephosphateuridylyltransferase galU P32501 (Saccharomyces) MG458Hypoxanthine-guanine 0565 Hypoxanthine phosphoribosyltransferase hptP00492 (Human) Phophoribosyltrnsfrse Regulatory Functions MG024 GTPase1520 GTPase ychF P38746 (Saccharomyces) MG335 GTPase 0530 GTPase yihAMG384 GTPase 0294 GTPase yhbZ P38860 (Saccharomyces) MG387 GTPase 1150GTP-binding protein era P32559 (Saccharomyces) Transport and BindingPolypeptides MG015 Transport ATPase msbAp P34712 (Caenorhabditis) MG033Glycerol uptake facilitator (permease) 0107 Glycerol uptake facilitatorglpF CAB69639 (Schizosaccharomyces) MG042 Spermidine-putrescinetransport 0750 Spermidine/putrescine transport ATPase potA CAA17820(Schizosaccharomyces) ATP-BP MG043 Spermidine-putrescine transport 0749Spermidine/putrescine permease potB permease MG044 Spermidine-putrescinetransport 0748 Spermidine/putrescine permease potC permease MG045Spermidine/putrescine periplasmic 0747 Spermidine/putrescine-bindingperiplasmic potD binding protein MG065 Transport ATPase MG071Cation-transporting ATPase MG077 Oligopeptide transport permease 0535Oligopeptide permease oppB MG078 Oligopeptide transport permease 0534Oligopeptide permease oppC MG079 Oligopeptide transport ATP-BP 0533Oligopeptide transport ATPase oppD P33311 (Saccharomyces) MG080Oligopeptide transport ATP-BP 0532 Oligopeptide transport ATPase oppFP33311 (Saccharomyces) MG119 Carbohydrate Transport ATPase 0240Galactoside transport ATPase mglA CAC00467 (Leishmania) MG120 Sugarpermease/ribose transport 1625 D-ribose ABC transporter rbsCp CAC08238(Schizosaccharomyces) permease MG180 Amino acid transport prt 0593Dipeptide transport ATPase dppF S51433 (Saccharomyces) MG187Glycerol-3-phosphate transport ATPase ugpC P21449 (Cricetulus) MG247Permease 1400 Membrane protein ygiH MG270 Lipoate-protein ligase lplANP_012489 (Saccharomyces) MG287 Acyl-carrier protein 1288 Acyl carrierprotein acpP ASYP (Spinacia) MG322 Na+ ATPase subunit J MG333 Acylcarrier protein phosphodiesterase 0769 Acyl carrier proteinphosphodiesterase acpD MG410 Phosphate transport ATPase 0784 Phosphatetransport ATPase pstB P13568 (Plasmodium) MG411 Phosphate permease 0785Phosphate permease pstA Particle Division MG224 Cell division protein0555 Cell division, GTPase ftsZ P29516 (Arabidopsis) MG297 Cell divisionprotein 0184 Cell division, signal recognition particle ftsY P20424(Saccharomyces) GTPase MG353 DNA-binding protein MG457 Cell divisionprotein 0737 ATP-Zn dependent protease ftsH P39925 (Saccharomyces)Polypeptide Chaperones MG019 Heat shock protein 0647 DnaJ chaperone dnaJNP_014335 (Saccharomyces) MG048 Signal recognition particle GTPase 1244Signal recognition particle GTPase ffh P37107 (Arabidopsis) MG055Preprotein translocase subunit 0131 Preprotein translocase subunit secEMG072 Preprotein translocase 0325 Preprotein translocase, putativehelicase secA Q06461 (Antithamnion) MG138 GTP-binding membrane protein1153 Membrane GTPase lepA P34617 (Caenorhabditis) MG170 Preproteintranslocase 0214 Preprotein translocase subunit secY MG201 Heat shockprotein 1209 Heat shock protein grpE CAA17799 (Caenorhabditis) MG210Prolipoprotein signal peptidase 0422 Lipoprotein signal peptidase lspAMG305 Heat shock protein 0646 DnaK Chaperone dnaK P41753 (Achlya) MG392Heat shock protein 1665 GroEL Chaperone groL P40413 (Saccharomyces)MG393 Heat shock protein 1664 GroEL Co-Chaperone groS Fatty Acid andPhospholipid Metabolism MG114 Phospatidylglycerophosphate Synthase 1260Phospatidylglycerophosphate Synthase pgsA P06197 (Saccharomyces) MG2121-acyl-sn-glycerol-3-phos 0149 1-acyl-sn-glycerol-3-phos plsC P33333(Saccharomyces) acetyltransferase acetyltransferase MG437CDP-diglyceride Synthase 0335 CDP-diglyceride Synthase cdsA NP_009585(Saccharomyces) Particle Envelope MG059 LPS-heptosyl-2-transferase 0399Complement SmpB smpB MG060 Lipopolysachharide biosyn protein yibDp motifMG086 Prolipoprotein diacylglyceryl lgtp transferase HousekeepingFunction MG125 Hydrolase 1140 Hydrolase yidA MG265 Hydrolase 0013Hydrolase yigL NP_011974 (Saccharomyces) MG295 ATP-utilizing enzyme(GuaA family) 1308 ATP-utilizing enzyme ycfB P00966 (Human) MG383 NH3,ATP-dependent NAD synthetase proSp CAA19255 (Schizosaccharomyces)

[0214]

1 19 1 38596 DNA M. genitalium 1 taaaacaaaa aaaacaagta ttaatttaaacacaattaat gtgaatgaat ttccaagaat 60 aaggtttaat gaaaaaaacg atttaagtgaatttaatcaa ttcaaaataa attattcact 120 tttagtaaaa ggcattaaaa aaatttttcactcagtttca aataatcgtg aaatatcttc 180 taaatttaat ggagtaaatt tcaatggatccaatggaaaa gaaatatttt tagaagcttc 240 tgacacttat aaactatctg tttttgagataaagcaagaa acagaaccat ttgatttcat 300 tttggagagt aatttactta gtttcattaattcttttaat cctgaagaag ataaatctat 360 tgttttttat tacagaaaag ataataaagatagctttagt acagaaatgt tgatttcaat 420 ggataacttt atgattagtt acacatcggttaatgaaaaa tttccagagg taaactactt 480 ttttgaattt gaacctgaaa ctaaaatagttgttcaaaaa aatgaattaa aagatgcact 540 tcaaagaatt caaactttgg ctcaaaatgaaagaactttt ttatgcgata tgcaaattaa 600 cagttctgaa ttaaaaataa gagctattgttaataatatc ggaaattctc ttgaggaaat 660 ttcttgtctt aaatttgaag gttataaacttaatatttct tttaacccaa gttctctatt 720 agatcacata gagtcttttg aatcaaatgaaataaatttt gatttccaag gaaatagtaa 780 gtattttttg ataacctcta aaagtgaacctgaacttaag caaatattgg ttccttcaag 840 ataataaatt tagtttgtgg caaaagcttctgtactgttt atttaatgga agaaaataac 900 aaagcaaata tctatgactc tagtagcattaaggtccttg aaggacttga ggctgttaga 960 aaacgccctg gaatgtacat tggttctactggcgaagaag gtttgcatca catgatctga 1020 gagatagtag acaactcaat tgatgaagcaatgggaggtt ttgccagttt tgttaagctt 1080 acccttgaag ataattttgt tacccgtgtagaggatgatg gaagagggat acctgttgat 1140 atccatccta agactaatcg ttctacagttgaaacagttt ttacagttct acacgctggc 1200 ggtaaatttg ataacgatag ctataaagtgtcaggtggtt tacacggtgt tggtgcatca 1260 gttgttaatg cgcttagttc ttcttttaaagtttgagttt ttcgtcaaaa taaaaagtat 1320 tttctcagct ttagcgatgg aggaaaggtaattggagatt tggtccaaga aggtaactct 1380 gaaaaagagc atggaacaat tgttgagtttgttcctgatt tctctgtaat ggaaaagagt 1440 gattacaaac aaactgtaat tgtaagcagactccagcaat tagctttttt aaacaaggga 1500 ataagaattg actttgttga taatcgtaaacaaaacccac agtctttttc ttgaaaatat 1560 gatgggggat tggttgaata tatccaccacctaaacaacg aaaaagaacc actttttaat 1620 gaagttattg ctgatgaaaa aactgaaactgtaaaagctg ttaatcgtga tgaaaactac 1680 acagtaaagg ttgaagttgc ttttcaatataacaaaacat acaaccaatc aattttcagt 1740 ttttgtaaca acattaatac tacagaaggtggaacccatg tggaaggttt tcgtaatgca 1800 cttgttaaga tcattaatcg ctttgctgttgaaaataaat tcctaaaaga tagtgatgaa 1860 aagattaacc gtgatgatgt ttgtgaaggattaactgcta ttatttccat taaacaccca 1920 aacccacaat atgaaggaca aactaaaaagaagttaggta atactgaggt aagaccttta 1980 gttaatagtg ttgttagtga aatctttgaacgcttcatgt tagaaaaccc acaagaagca 2040 aacgctatca tcagaaaaac acttttagctcaagaagcga gaagaagaag tcaagaggct 2100 agggagttaa ctcgtcgtaa atcaccttttgatagtggtt cattaccagg taaattagct 2160 gattgtacaa ccagagatcc ttcgattagtgaactttaca ttgttgaggg tgatagtgct 2220 ggtggcactg ctaaaacagg aagagatcgttattttcaag ctatcttacc cttaagagga 2280 aagattttaa acgttgaaaa atctaactttgaacaaatct ttaataatgc agaaatttct 2340 gcattagtga tggcaatagg ctgtgggattaaacctgatt ttgaacttga aaaacttaga 2400 tatagcaaga ttgtgatcat gacagatgctgatgttgatg gtgcacacat aagaacactt 2460 ctcttaactt tcttttttcg ctttatgtatcctttggttg aacaaggcaa tatttttatt 2520 gctcaacccc cactttataa agtgtcatattcccataagg atttatacat gcacactgat 2580 gttcaacttg aacagtgaaa aagtcaaaaccctaacgtaa agtttgggtt acaaagatat 2640 aaaggacttg gagaaatgga tgcattgcagctgtgagaaa caacaatgga tcctaaggtt 2700 agaacattgt taaaagttac tgttgaagatgcttctattg ctgataaagc tttttcactg 2760 ttgatgggtg atgaagttcc cccaagaagagaatttattg aaaaaaatgc tcgtagtgtt 2820 aaaaacattg atatttaagt agtgttaaaaacattgatat ttaatttggt tagtataaat 2880 ggcaaagcaa caagatcaag tagataagattcgtgaaaac ttagacaatt caactgtcaa 2940 aagtatttca ttagcaaatg aacttgagcgttcattcatg gaatatgcta tgtcagttat 3000 tgttgctcgt gctttacctg atgctagagatggacttaaa ccagttcatc gtcgtgttct 3060 ttatggtgct tatattggtg gcatgcaccatgatcgtcct tttaaaaagt ctgcgaggat 3120 tgttggtgat gtaatgagta aattccaccctcatggtgat atggcaatat atgacaccat 3180 gtcaagaatg gctcaagact tttcattaagatacctttta attgatggtc atggtaattt 3240 tggttctata gatggtgata gacctgctgcacaacgttat acagaagcaa gattatctaa 3300 acttgcagca gaacttttaa aagatattgataaagataca gttgacttta ttgctaatta 3360 tgatggtgag gaaaaagaac caactgttctaccagcagct ttccctaact tacttgcaaa 3420 tggttctagt gggattgcag ttggaatgtcaacatctatt ccttcccata atctctctga 3480 attaattgcg ggtttaatca tgttaattgataatcctcaa tgcacttttc aagaattatt 3540 aactgtaatt aaaggacctg attttccaacaggagctaac attatctaca caaaaggaat 3600 tgaaagctac tttgaaacag gtaaaggcaatgtagtaatt cgttctaaag ttgagataga 3660 acaattgcaa acaagaagtg cattagttgtaactgaaatt ccttacatgg ttaacaaaac 3720 taccttaatt gaaaagattg tagaacttgttaaagctgaa gagatttcag gaattgctga 3780 tatccgtgat gaatcctctc gagaaggaataaggttagtg attgaagtaa aacgcgacac 3840 tgtacctgaa gttttattaa atcaactttttaaatcaaca agattacaag tacgcttccc 3900 tgttaatatg cttgctttag ttaaaggagctcctgtactt ctcaacatga aacaagcttt 3960 ggaagtatat cttgatcatc aaattgatgttcttgttaga aaaacaaagt ttgtgcttaa 4020 taaacaacaa gaacgttatc acattttaagcggactttta attgctgctt taaatattga 4080 tgaggttgtt gcaattatta aaaaatcagcaaataaccag gaagcaatta atacattaaa 4140 tacaaagttt aagcttgatg aaattcaagctaaagcagtt cttgacatgc gtttaaggag 4200 cttaagcgta cttgaagtta acaaacttcaaactgaacaa aaagagttaa aagattcaat 4260 tgaattttgt aagaaagtgt tagctgatcaaaaattacag ctaaaaataa tcaaagagga 4320 attgcaaaaa atcaatgatc agtttggtgatgaaagaaga agtgaaattc tctatgatat 4380 ctctgaggaa attgatgatg aatcattgataaaagttgag aatgtagtga taactatgtc 4440 tacaaatggt tatctaaaaa ggattggagttgatgcttat aatcttcaac atcgtggtgg 4500 agttggggtt aaagggctaa ctacttatgttgatgatagt attagtcaat tattggtctg 4560 ttcaactcac tctgacttat tattttttactgataagggt aaggtttata gaattagagc 4620 tcatcaaatt ccctatggtt ttagaacaaataaaggtatt cccgctgtta acttaatcaa 4680 aattgaaaag gatgaaagaa tttgttcattgttatctgtt aataactatg atgatggtta 4740 tttctttttc tgtactaaaa atggaattgttaaaagaacg agcttgaatg aattcatcaa 4800 catcttaagt aatggtaagc gggctatatcttttgatgat aatgacactt tgtattcagt 4860 aattaaaacc cacggaaatg atgagatttttattggttct accaatggat ttgttgttcg 4920 cttccatgaa aatcaactca gagttctttcaagaacagca agaggtgtat ttggtatcag 4980 tttaaataaa ggagaatttg ttaatggactatcaacttca agcaacggta gcttactttt 5040 atcagtcggt caaaatggaa taggtaaattaacgagcata gataaatata gactcacaaa 5100 acgtaatgct aagggagtta aaactctaagggttactgat agaacaggcc ctgttgttac 5160 aacaaccact gtttttggta atgaggatcttttaatgatt tcctctgctg gtaaaattgt 5220 gcgtaccagt ttacaagaac tttcagaacaaggtaaaaac acttctggtg ttaagttaat 5280 tagattaaaa gataatgaac gtttagaaagagtaactatc tttaaagaag agttagaaga 5340 caaagaaatg caactagaag atgttggatccaaacaaatt acgcaataat taaacattaa 5400 ccgtcaacaa caagaaactt tatagagcaatgaaaaatca aaccaagagt aatagtttat 5460 ttcaactttc cactaactat atacctactggtgatcaacc tgaagcaatt aagaaattat 5520 cagaatttaa aactaagcag caggttttattgggggccac aggcacaggt aaaaccttta 5580 caattgctaa tgtaattcaa aacagccaactcccaacagt tgttattgct cataacaaaa 5640 ccctagcagg tcaactcttc aatgaattaaagcaactgtt tcctaaaaat gcagttgaat 5700 attttatctc ttactttgat ttttatcaacctgaagctta cttacccagt aaagggatct 5760 acattgaaaa aagtgctaca gtcaatgaagcgattaaacg cttaagagtc tcaacactgc 5820 attcactttc aacaagaaaa gatgttattgtagtaggttc tgttgctagt atttatccca 5880 cctcatctcc cagtgatttt gttaagtattgcttgtggtt tgtggttggc aaagattatg 5940 atttgaaaac cattaaagat aggttagttagtcttaacta tgttgttaat aaacaacaat 6000 taaccccagg aaaatttcgc tttcagggtgatgttttgga ggtatttcct ggttacagtg 6060 atgcttttgt gatcagaatc tccttttttgatactaaagt agaacaaatt tgtcaaattg 6120 acccactaac aaataagatt ttaaaccaactctttgagat taagataggt cctgctgatg 6180 aatatgttgt aaaccaatct gatcttgatatagcaattaa aaatattaaa caagaacttc 6240 aggaacgagt taattatttc aataagcaaaatcttgttga aagagcacaa cgtttagcca 6300 ccattactaa ccatgatctc aatgatctgaaggcttgggg attttgtagt ggagttgaaa 6360 actatgctag acacttagag ttgaggatggctaactcaac cccttacagt atctttgatt 6420 attttaaggg ggattggtta ctggttattgatgaatcaca ccaaacttta ccgcaactta 6480 atgggatgta taacactgat ctttcaagaaagcaaagctt aattgattat ggttttcgac 6540 tcccctctgc acttgataac agaccgctctcatttgctga attacaacaa aaaatgcaaa 6600 aagttattta tgtttcagca actccaagagataaagagat tagtttaagt cagaataatg 6660 tcattgaaca gttagttaga ccaacttacttggttgatcc tattatcgtt gttaaaccaa 6720 aagataacca ggtggaggat ctcattgaagagattatcaa ccaacgccaa aacaacacaa 6780 gaacatttgt tactgtttta actattaagatggctgaaaa cctcactgaa tacttaaagg 6840 aacgcaaaat taaagttgcc tatatccataaggacattaa agcattggaa cgtttattgt 6900 taattaatga cctgagaaga ggtgaatatgagtgtttagt tgggattaac cttttaagag 6960 aagggttaga tgtccctgaa gttgctttagtttgtatctt tgatgcagat atcccaggac 7020 tacctaggga tgagagaagt ttaatccagattattggacg tgctgctaga aatgaacatg 7080 gtcgagttgt tatgtatgct aaccatgttactgaacagat gcaaaaagcc attgatgaaa 7140 ccaaaagaag aagaactgtt caaatggaatataacaagct acataataag acaccaaaaa 7200 cagttgttaa accccttacc tttgttcaaccaatcaaatt aaaagctaag agtaatgcag 7260 aaaaaaatgc tgcattaatc aaacaattaaccaaagaaat gaagaaagca gcagctaatc 7320 aaaattatga acttgccatt gagattagagattccatatt tgaattggaa aaagaaattg 7380 gtagtaaaat taaagtatag tcgttttcaaaatcaattta aaaaaggagc aaaaccttag 7440 atgaaccggg tcttcttgtt tggtaaactcagttttactc ccaaccgttt acagacaaaa 7500 aatggtacgt taggagctac tttttccatggaatgtcttg attccagtgg ttttaataat 7560 gccaaatcat tcattagagt aactgcttgaggtaaagttg ctagttttat tgttgctcaa 7620 aatcctgggg tgatgctttt tgtagaaggaagattaacta catataaaat tactaacagt 7680 gaaaataaaa acacctatgc tttacaagtaactgctgata agatctttca tcctgatgaa 7740 aaaactacca atgaagaacc tattaaatcaactgtagttg attcaccctt tatgaatccc 7800 aaagcaagtg ttacagaagc tgagtttgaacaagcattcc cccatcaaga tgaaactgat 7860 tttaacaaca ttacccctat atttgaaaatgatgtccaac tagaggagga aagtgatgat 7920 taatgcaaat gatagcaaca ttgaacgtgctgaaagacgt ttgatgcaag cagttgctca 7980 aaacagtgag ggcattgatc taattttcaataaacttgaa ccaattgatt tttttgcaac 8040 ccctttcaaa ctcatttttc aaactgcaaaagaaaactac caattaaata accctattat 8100 tggttctggt ttactagaag cggttaagtttaaacttgat gctaatgatc aatccactaa 8160 aagtgaactt gaaattttat tcacaaagatcttattaatc cgtttaccac ctaaccaaac 8220 agagattaaa acactggttg atgttgttaaaaaagcttct atttttcgca ggttacaaca 8280 gtttgctaag cgtgtttaca acgaggaatttaagttaaaa gaagatcgtt ttgaaggcta 8340 tttacaagct attcaagatg attttgtcaagattatccac agtgctttta gtaacatctt 8400 tgcttttagc tatgatgaga ttgccaatcaagaggaagca ttaattaaaa aggttcaccg 8460 tggggaattg atcatcagtg gactttcaagtggattttta aaattagatc aacttacatc 8520 aggttgaaaa ccaggagagt taatagtaatagcagctcgc ccaggtagag gtaaaactgc 8580 ccttttgatt aattttatgg ctagtgcagctaaacaaatt gatcctaaaa ctgatgtggt 8640 cctcttcttt agtttagaga tgcgtaaccgggaaatttac caaaggcact taatgcatga 8700 aagtcaaact agttacacac taaccaaccggcaaaggatt aataatgtct ttgaagagtt 8760 aatggaagca tcttcaagga tcaaaaacttacctattaaa ctctttgatt acagtagttt 8820 aacactccaa gagatcagaa accaaattactgaagtgagt aaaaccagta atgttaggtt 8880 agtaattatt gactatttac aacttgttaatgctttaaaa aataactatg gtttgacaag 8940 acaacaagaa gtgacaatga tctctcaatcacttaaagca ttcgctaagg agtttaatac 9000 ccctattatt gctgcagctc aactttctagaaggattgaa gaaaggaaag attccagacc 9060 aattctttct gatttaagag aatcaggttcaattgaacag gatgcggata tggttttatt 9120 tatccataga actaatgatg ataaaaaagaacaggaagag gagaacacaa acttgtttga 9180 agtggagctt atcttagaaa agaacagaaatggtcccaat ggcaaagtta aactaaactt 9240 tcgcagtgac acttcttctt ttattagtcaatattcccct agttttgatg accaatacag 9300 ttaatgatca gttactttta cctagataaatttaaagttt atttgtggta atggatgatc 9360 tattccaaag aatggttagc tgtgttctaccgtcatgaag agcttttatt gatgaggaag 9420 ttaaaaaacc ttattttcaa gctttattagaaaaattaaa ggctttaaaa gcaacaataa 9480 ttccaaaacc agaacttatt ttccgtgtttttagcttctt taagccaatt gatacaaagg 9540 taattatctt tggtcaagat ccctatcctagtcctaatga tgcttgtgga cttgcttttg 9600 catccaataa ttccaaaacc cctgccagcttaaaaagaat aattttacgt ttagaaaaag 9660 aatatccttc gcttaaacaa gaaagtagttgacaacaaaa cttcctattg aattgagcag 9720 aacagggcgt tttattacta aatggaattttaacaactac tgtatttata cgcaacgccc 9780 ataaaaattg gggttgggag gagtttaactgtaatttgct aacttttcta aaaaatcaaa 9840 acattaaacc gctgttggta tttctgggtgttcaaactaa aaactttgtt gttaagagta 9900 ttggtaatgt tgatggattt gagcatttatcatatcccca tccctcacca ctaagtggta 9960 atttgtttct aacaaaccct aacgatctgtttaaaacaat taacaattgg ttgaaacaac 10020 ataaccaaaa aataattaac tgagcagttgttaaaaatgc tagttttgac caattaagtt 10080 aaaacaaaaa ccttatttat agttaagtaagtagttttat taatgattaa aaacctggtg 10140 gtgattgaat cacccaataa agttaaaacattaaaacaat atcttcctag tgatgaattt 10200 gagatagtct caaccgttgg tcacatcagagaaatggtgt ataaaaactt tggttttgat 10260 gaaaatacct atacccctat ctgagaagattgaactaaaa ataaacagaa aaatcccaaa 10320 cagaaacacc tgctcagtaa gtttgagatcatcaaatcaa tcaaagctaa agctagtgat 10380 gcacaaaaca tttttttagc ttctgaccctgatagagaag gggaagccat ctcttggcat 10440 gtctatgatt tattggatca aaaagataaagctaagtgca aacgaatcac tttcaatgag 10500 atcactaaaa aagcagtagt agatgcattaaaacaaccgc gtaacatcga tcttaactgg 10560 gttgaaagtc agtttgcccg ccaaatccttgacaggatga taggttttag attatcaaga 10620 ttattaaata gttatctgca agcaaagtctgcaggtagag ttcaatcagt ggctttgcgc 10680 tttcttgagg aaagagaaaa ggagatagctaagtttgttc cgcgtttttg gtggacagtt 10740 gatgttttat taaacaaaga aaataaccaaaaagtagttt gtgcaaacaa gtctattcct 10800 ttggttttaa gagaaattaa ccctgaattaagtgctagtt taaaactgga ttttgaagct 10860 gctgaaaacg tatcaggaat tgactttttaaatgaagctt cagcaaccag atttgccaac 10920 caactgactg gcgaatatga agtttattttattgatgaac ctaagattta ctattcatct 10980 ccaaacccag tttataccac cgcttcacttcaaaaggatg caattaataa gttaggatgg 11040 tcttccaaaa aagtaacaat ggtggcccaaagactgtatg aagggattag tgttaatggg 11100 aaacaaactg cattaattag ttatccaagaactgattcaa ttaggatttc aaaccaattt 11160 caatcagagt gtgaaaagta cattgaaaaggagtttggaa gtcattattt agctgataaa 11220 aataagttaa aaagacataa aaaggatgagaaaatcatcc aagatgccca tgaagggatc 11280 catcctactt acattactat tacccccaatgatctgaaaa acggggtgaa acgcgatgag 11340 tttctccttt atcgtttaat atggattagaacagttgcta gtttaatggc agatgctaaa 11400 acatcaagaa ctattgttcg ttttataaaccaaaaaaaca agttttatac ctcttcaaaa 11460 tcacttttat ttgatggtta tcaaaggttatatgaagaga ttaaacctaa tactaaagat 11520 gaactttaca ttgatcttag taagcttaaaattggtgata aatttagttt tgaaaagatc 11580 agcgttaatg agcataaaac caacccaccaccacgttaca cccaagctag tttaattgaa 11640 gagcttgaaa aatctaacat cggtcgtccctctacttata acactatggc cagtgttaat 11700 ctagaaaggg gctatgctaa cttagtgaaccgattttttt atatcactga gcttggtgaa 11760 aaagttaata atgaactttc caagcattttgggaatgtaa ttaataaaga atttaccaag 11820 aagatggaaa aatctttgga tgaaattgctgaaaacaaag taaactatca agaatttctt 11880 aagcagtttt gaacaaattt taaatctgatgttaaactag ctgaaaattc aattcaaaaa 11940 gtgaaaaagg aaaaagaatt ggttgaaagagattgtccta aatgtaatca accgttggta 12000 tatcgttaca ccaaaagagg taatgagaagtttgttggtt gtagtgattt tcctaagtgt 12060 aaatacagtg agtttagtaa tcctaaaccaaaactaacct tggaaacact tgatgaattg 12120 tgtcctgagt gtaacaataa actggttaagaggagaacta aatttaacgc taaaaagacc 12180 tttataggtt gcagtaattt ccctaactgccgttttatca aaaaggataa tgctgctgaa 12240 tttaaacaat aacggcagca aagctaatttcaattttaaa ttcaaacttt agatgaaaag 12300 taactacagt gcaactaaca tcaagatcttaaagggtttg gatgcagtta aaaagcgtcc 12360 ggggatgtac attggttcta ctgatagtaagggtctgcac cacatgctat gggaaattct 12420 tgctaacagt gttgatgaag ttttagctggttatgcaacc aatattactg ttactttaga 12480 tctcaacaac accattactg ttagtgatgatggcaggggt attccctatg agatccacca 12540 agacagtaac atctctacga tcgatacagttttcaccttt ctccatgcag gggggaagtt 12600 tgatgatcag tcatacaaac tagcagggggattacatggg gttggtgcat cagtggtcaa 12660 tgccttaagt gatcatttag aagtaacagtgaaaagaaat ggtcagatct accaatcagt 12720 ttatcaagct gggggtaaga tcatccaaaaagccaaaaag attggtgata caactagcca 12780 tggtaccact gttagtttcc atgctgaccctaaggtcttt aaaaaggctc aatttgatag 12840 caacattatt aaaagcaggt taaaagagctaagctttctg tttgctaaac taaagctcac 12900 ttttactgat caaaaaacta ataaaaccactgtttttttt agtacctcag gactagttca 12960 gttccttgat gaaattaata atactgtagaaacacttggc caaaaaacac tgattaaagg 13020 tgagaaggat gggattgaag tggaagtggttttccagttt aaccaatcag atcaagagac 13080 aatcttatca tttgctaact cgattaaaacctttgaagga gggagtcatg aaaatgggtt 13140 ttgtcttgcc attagtgatg tgatcaacagctattgcaga aagtacaact tactaaaaga 13200 aaaagataaa aactttcaac ttagtgagatcagacaaggg ttgaatgcta ttatcaaagt 13260 taacttacct gaaaaaaaca tcgcttttgaaggacaaact aagagtaagt tgttttcaaa 13320 ggaagtgaaa aacgttgttt atgaattggtccaacaacac tatttccagt ttctggaaag 13380 aaacaacaat gatgctaaat tgatcattgataaactactc aatgctagaa agattaaaga 13440 gcaaatcaaa caacaacgtg agttgaaaaaaagtttatca agtccccaaa aagagaagat 13500 cttatttggg aagttagcac cttgtcaaaccaaaaaaacc agtgaaaaag agttgtttat 13560 tgttgaaggt gatagtgctg gtggcactgctaaaatgggc cgtgatagaa tttttcaagc 13620 tatcttacct ttgcgcggca aggtgttaaatgttgaaaaa attaacaata agaaggaagc 13680 gatcactaac gaagagatcc tcactttaatcttttgtatt ggtacaggga ttttaactaa 13740 cttcaacatc aaggacttaa agtacggaaagatcatcatt atgactgatg cagataatga 13800 tggcgcacac atccaaatcc tcttacttaccttcttttat aggtacatgc aacccttaat 13860 tgaactgggc catgtctatc tagctcttcctcctttatat aaactggaaa ccaaagatag 13920 aaaaacagtt aaatacctct ggagtgatttggagttggaa tcagtcaaac taaagcttaa 13980 taacttcact ttacaacgat acaaaggacttggagagatg aatgctgatc agttgtgaga 14040 tactactatg aatccaacta ccagaaagctagtgcaagta aagcttgatg atctaattaa 14100 cgctgaaaag caaatcaaca tctttatgggtgaaaagagt gatttgcgca aacactggat 14160 tgaagccaac attaacttta gtgtggaaaactaaatggat caaaaaaaca acaacctctt 14220 tcaaaaggca attgaagaag tctttgcagttagctttagt aagtatgcta aatacatcat 14280 ccaagataga gctttacctg atctaagagatgggttaaaa ccagtacaaa gacggatctt 14340 atatgggatg tttcaaatgg gcttaaaacccaccactccc tataaaaaat cagcccgtgc 14400 tgttggggag atcatgggga aataccacccccatggtgat agttccattt atgatgcaat 14460 tatcagaatg tcccaaagct gaaagaacaactgaacaact gtttctatcc atggtaacaa 14520 tggttcagtg gatggggata atgctgcagcaatgcgttac acagaaaccc gcttaagctt 14580 gtatggattt gaactattaa aagacattgataaaaagtta gttagtttta tcaataactt 14640 tgatgatagt gaaaaagaac caacggttttaccaacctta ctgcctaacc tctttatcaa 14700 tggtgcgagt gggatagctg ctggatatgcaactaatatt gctccccata acactaatga 14760 actattagat agtctttgct tgcgaatagaccaacctaat tgtgaactta aacaaatttt 14820 aaaaattgtt aaaggtcctg attttccaacagggggtaat gtttattttg aaaagagttt 14880 aagtgatatt tatcaagcag gcaaaggtaaatttattatc caagctaagt atgaagttaa 14940 caagaactta aaccagattg aaattacccaaatcccttat gaaacactga aagctaacat 15000 tgtcaaacaa attgaagaga ttatctttgacaataaacta tctgctattg aaagtgtcat 15060 tgatagttca gatcgcaacg gcattaggatcattattaaa cacaaggact ttttgcctgc 15120 tgagaagatc atggcctttt tgtttaaacacacccaactc caagtgaact ttaaccttaa 15180 taacaccgtg attgctaacc gctttcccatccaaattggt ttactaagtt acctcgatca 15240 ttttttaaag ttttgtcatg aactaattattaataaagct aagtatgaac ttgagcttgc 15300 aagcaagcgc ttggaaatta ttttaggactaattaaagcg attagtatca ttgataaaat 15360 catcaaatta attagatcag cagttgacaaaagtgatgca agagaaaagt taattgataa 15420 ctttaaattt acttttaacc aagcagaggcaattgttagt ttgcgacttt accaactaac 15480 taacactgat atttttgaac ttaaccaagaacaaaatgaa cttgaaaaaa ctgtgattag 15540 ttcagagcaa ctaattgcta gtgaaaaagcaagaaacaaa ctcctaaaaa aacagtttga 15600 aggttataaa aagcagtttc accagcaacgaaggtcacaa atatgtggct ttattaacca 15660 aaaaaaggtg gaggaaagtg agctaattgaaaacaaaact tatggggttt taatcactaa 15720 agctggtaac taccataagt ttgaatctaaccaactatta aaaagcacca ctgattttaa 15780 aagtgagagt gacacaatta tctttgcacaaactattgct aataccgacc aaatttttat 15840 tgtcacttca ctaggtaaca ttattaatatccctgtttat aaattagctt tcaattccaa 15900 aaataaacta gcaagtttag ttagtaaaaaaccaatcctt ttggagtatg aaacgattgt 15960 ttttgttgga acaatgaaca gtgtaaaccaaccaatcctt gttttaactt ccaaactagg 16020 aatggttaaa cggattgatt taaccaaacttaacattaag ccacttaaag ctactttgtg 16080 tatctcactc cgtgataaag accatttagtaagtgcattt ttacaacaag atgataaact 16140 gatctgttta gtgtctgatc acaactattacactgttttt cacaccaatg agatcccatt 16200 aattagtagt aaggggatgg gagtgaaggggatgaagtta aaactagagg atcaaattaa 16260 gtttgttgtt gcttttgaag ctaatgaaccgttagtgatg atatgtagtg atggtagtgt 16320 cattaactta aaacaaactg aactagttgtagttagcagg atggcaactg caaaaaaact 16380 gcctgttaag aaagcaatta actattgttttagtgatgca actaacaccc agttaattaa 16440 ttttcagggt aagaacggta gtaaattaattacaactagt gaactgaacc agatgagtaa 16500 aactgcaatt agtcaaacca ggtttaacaaacttaattag tgcacctcac caaaaaaacc 16560 acccgtgctt ttattttcag atgggtttatgtatggggca atgtatgcaa actgatacta 16620 aggaaaaata ccaacaggta attagtaacattgaacagtt ttttaatgac cctagtgtgg 16680 taattaacta tttaaaagct gcagaaaaaaaggcaagtga taatcaggaa tttgaaaagg 16740 cccagcagtt tctaacactg caaaaagcagttttagagtt aacaaaaacc caccatacca 16800 ctatcattaa acaaaaatca agccatgattttattgggta tgtctttcaa aataacgttt 16860 tggccattac cattttttgt tatgaaaaaggggagttaac tgataaagaa caagcagtgt 16920 ttaccctaga gcaaactgac attgtggaagttgaaagtgc tattatcacc tttatctacc 16980 accactataa aactacccca cttccaagtaagattactgt ttcacttgat gaaactaacc 17040 taaaacttat tagtgatagc ttaaaaattggtgtttttaa gcccaagaat ggtaatgaaa 17100 aactgatctt acaaactgtt attgataatgccaaacatgc acttgcaacc aagtggttga 17160 agtttactag taactatgat aaaacccagctccacaagga tttagcacaa cttctaaata 17220 ctgattatat ccatagtctt gagattattgatgtgtcatt ctatgatcaa aaccatgttg 17280 ttggttgcat gttaaggttt gaagatggtaaaaagatcaa acacttatca agaagataca 17340 acattaacag tttaaaaaaa ggtgatactaaccacattgc tttacttgtt tacagaagga 17400 tcttaagtgc gatgcaaacc aaagctaacctcccttttag tgatctttta attattgatg 17460 gtggtaaagc acaaattaaa agtgttaagcaagtttttag tctcttcagt aatgttaaac 17520 cacccattat cattggacta gttaaaaacaaaaaccacca aactgatcac attatgttat 17580 ctgatttcca agttaaaaag atagcaattaactccccact ctttcactat ttagcaacaa 17640 tccaaactga agttgatggt tttgctaaaagaagtgcttt taataagtta agtaaccacc 17700 aactgcaaaa cccgttgcta caaatcccaggagttggcaa gataactgcc caaattctct 17760 ttgataactt tcaaacgctc aataacataaaattagcttc agttaatgag ttaagccagt 17820 ttattaaaaa accattagca caaaagattaaaacttactt tgcaaaacaa actgattaat 17880 agctcttgat gaagtggaaa aactcattaattaataacaa tgaatgaaca acaaaaacaa 17940 gcaattagtt gtggaaaagg ggttaatgttgtttattctg gagcaggtac tggtaaaaca 18000 acaattatta ctaatcgctt tgcatacttggttaataaag aaaaagttga tcctagcaga 18060 attttagcaa tcacctttac taagaaagctgctaaggaga tgcagtttag aatcttgaaa 18120 ctaatagata gttctttagc tgagaaaacaaatatctata catttcacag cttttgcaat 18180 aagtttttaa ttcaaacatt aaaaaagcgctttatcatcg atgatgatat tagctatttc 18240 ctaaaggaat ttttagctga ttcaaaactcgatatcaacc tagcgaaaca aattattgat 18300 aactttaaaa atacttttgc tgattttgaaataaataagt tggatcaaga tgaaaggtta 18360 attagtttat gtgagcattc acttctaaataaagatgaag aatattccac tttaaaaacc 18420 caactgatta atgcattcat tagctatgaaaagaataaga tattaaacaa taaacttgat 18480 tttcatgatc ttttaattaa aacttgtaatttattgagta atgataatga tttacttaat 18540 cagtggagtg aacagtttca gcatattttagttgatgaat ttcaagatac caaccaaatc 18600 caatatgaac tgatcaagat gttagtaactaaaaataaaa acttgttttt ggtaggtgat 18660 aataaccaga tgatttaccg ctgaagaggggcggtaaacg ggatcataac tgctttaaag 18720 catgacttta atgttccgaa aagcaatgaattctttatta atcaaaatta ccgttgcgat 18780 cagaatattt tagcagttgc taaccaaattcttttaaaaa ttatggccta tgaaaaacaa 18840 gttaaaactg aaaaaaatct cttgttttcaactttaaatt ctgataaaaa acctgtttat 18900 tttcaagctg aatcagttga aaatcaagccaattggatct tcaataaaat caaagcacta 18960 aaccaaacag aaaagattaa ttttaaggatatggccatct tgtttagaaa gaacagagat 19020 attactacta tggttgaatt gattgaagcggatggaacaa ttcccttacc taaacaaaag 19080 agttatttta accaactagt aaaactccagcgggttttaa ttgcgatttc aaccagaaca 19140 aatcttgata ttaaaagagc tttgcaagccctaaaaattt gatcaaatga tttaaaggaa 19200 ttgtgaaaac agagtgataa aacaaacctatttgattttc ttaaatgatc agaattaaat 19260 caaaaaaacc atagttcaaa acttaaagctactggttatt ttaatctgct gattaagtta 19320 gcagaggatc agcaaattaa ccttttgtttactgaactgt ttaaaaaact caaagtggat 19380 caaactattg aaaatctgct ttgaaaaaaactaactgaat ttcaaaaaga taaaactgaa 19440 tttagcttat cagagtttat tactagcttagcattggaat ttgactcaat tattgaaaac 19500 agcagtgata caatcaattt gctaaccgttcatgcagcaa aaggacttga gtttgaagct 19560 gtatttattt atggcatgaa tcaaggggattttcccttat ttttaagtca aaatcaaaat 19620 gacgaacaac atttaattga tgaattaaaactgttttatg ttgctatcac aagagcaaaa 19680 cgttttttgt ttatcactgc ggttttacaaataaataaca attctataaa accatctagt 19740 tttttaaatt acatcaataa aagtgagtatttagacattg ctactattaa ctatgtatta 19800 gagcaggatg atgatttttt tgattcaactaaaaaaacag actatacaaa gaaactaaga 19860 aaagaaagtt tagacattat agtgggtgatttagttacta gtagatactt tggaaaagga 19920 gttgtagttg aagtgagaga caaagaggttttagtagctt ttaaagacac acgctatggg 19980 atgaaatgga tcttaaaaaa ccataaatcactaacaaaag ctttatatta acgaattgct 20040 atcaaagaat taccacaatg attcatgaaaaatggtcaat aaaagcaaca gtttagatga 20100 acttttaaag cagattaaaa ttactgaaattattcaacac tacggggtta aaatccaaac 20160 taagggtaat agtctacttg ctttatgtccttttcatgat gataaaaatc cttctatgtc 20220 catttccagt tctaaaaaca tctttaagtgttgggcttgt aatgcagctg gcaacggaat 20280 agcgtttatc caaaagcatg accagttagattgaaaaact gcacttaaaa aagcaattga 20340 aatttgtgga attaagttag aaaattggaacagtaattta ctaacaaaag ttgatccaaa 20400 acaaaaacga tattgggaga taaacaatgctttaattact tattatcaaa ccagattaaa 20460 aagagaaaca aacccaaatg ggatgaattatttagttgaa aaaagaaagc ttaataaaac 20520 attaattgaa cagtttcagc taggacttgcttttcacaat gaagataagt atctatgtga 20580 aagtatggaa agatacccct tcattaatccaaagataaaa ccgagtgaat tgtatctttt 20640 ttcaaaaact aaccagcaag gtcttggcttttttgacttt aataccaaaa aagctacctt 20700 tcaaaaccag attatgatcc ctatccatgactttaatggt aacccggttg gtttttcagc 20760 aagaagtgtt gataacatca acaaactgaaatataaaaat agtgctgatc acgaattttt 20820 taaaaaaggg gagctgttat ttaactttcacaggttaaat aaaaacctca atcaactctt 20880 tattgtggaa ggttattttg atgtttttacactaacaaac tccaagtttg aagctgttgc 20940 attaatggga ttagcattaa atgatgtgcaaattaaagcc attaaagctc actttaagga 21000 gttacaaacc ttagttttag cacttgataatgatgctagt ggtcaaaatg ctgtgtttag 21060 cttaattgaa aaacttaata acaacaattttattgtggaa attgttcagt gagaacacaa 21120 ctataaagat tgggatgaac tgtatttaaacaagggtagt gagcaagtta tattacaagc 21180 aaacaaaaga caaaatctaa ttgaatatcttgttagtttt tttaaaaagc aacaacttga 21240 tcaaagggtt attactaata aaatcattgcttttttaaca aaaaaccaaa caattttaaa 21300 cgaccatagt tttttaattt ttctcattaaaaatttggtt aaactacttg aatatagtga 21360 tgaaaaaact ctgtatgaaa cagttttaaaacacaaagaa aaacttgtat ctaagtttga 21420 taacaaccgt ttttacataa atacttcaggccatgctcaa ccaccacaag aattgcaaaa 21480 aaccactgca gcactagtgc aaacagcttttgaagaagca gttaatgagt tgtgaaaacc 21540 tgaaatcttt gcgtttgctt taattgataaacgctttttg gttgaattaa aacaatccca 21600 tctagatgaa gtttttaagg aatgtaactttaatttgttt gatgttgaac tttttattga 21660 aaaagcaagg atctattgga gtgaaaatcaaactgctaac tgagttggtt ttgaaagtgt 21720 tttagatcaa aattaccttt taaacaataaagcaaggtta ttggaaatta aagatatttt 21780 tttagatgaa ttaacttgtt atcaagctaatgattttcaa aactatctaa agacctttca 21840 aacgttatta aaacaacaaa agcagcgcttaaaaaattta aagttaacgc tataaattgg 21900 tatcaactaa gtcaggattt ttcttatttatagtagtgat ggatgtgaaa ttgaagattc 21960 aacagctggt taacttaata aaaaactatgactatcacta ctatgtttta agcgaacctt 22020 taattgatga ttttgagtat gatatgttgtataagtcact ccaacaatta gaaaaagatc 22080 atcctgattt aatccaaatt gattcccctacccaaagggt gggaggagaa gctgtgaagg 22140 gttttaaaaa gttaaaccat aacagtccaatgctctcttt ggaaaatgct ttttcaacta 22200 aagaaattgc taattttatt gataatattaactttcaaac aaactcaaaa aatgaatttg 22260 tagttgaacc taaaattgat ggagttagtatctctctaac ttataaaaat ggtgttttag 22320 ttcatgcttt aaccagagga gatggaagtgttggggaaga tgttttaaat aatgttaaaa 22380 ccattaaatc tatcccttta acaatccctttcacaaaaac aattgagatt aggggtgaga 22440 tttttgttga taaaaaaact tttttagcaattaacaatca acttgaaaaa ccatttgcta 22500 atgcaaggaa tctagcagca ggtacaatacgtaatttaaa cagtgaaatc actgcacagc 22560 gcaaattaag ggcattattt tattacatccctaatggttt ggaagagtca atcactactc 22620 aaactatggt tttagaacag cttaagcagtgaaaattccc agttagtgat accatcaggg 22680 tttttcaaaa caaatttcaa ttaattaattacttggaagc gtttgacaaa aaacgagaac 22740 agttaacttt taatcttgat ggtttagttattaaactaaa cagcttgctt ttttatcaac 22800 aattaggtgc tacaagtaaa tcaccacgttgggcaatagc atttaaattt agtcctaaat 22860 ttgttcaaac taaattaaca gcagttcttataacgattgg tagaactggt agagtgaact 22920 atactgctaa attagaaagt gttaatttagatggaacaaa agtaacagct gctactttac 22980 ataactttga ttacattaaa actaaagacattaggatcaa tgacactgtt gttatctata 23040 aagctgggga aattatccct aaagtactaaaggtaaatct tgaaaaaaga aaaaatgaca 23100 ctatcataat tcaagagcaa aaatattgtccttcatgtaa ttcaaaacta gtcaaaatag 23160 ttgatgaagt tgatcagtat tgtaccaatgaaacttgtaa ggagcgaaac atccagttaa 23220 ttaactattt tgtttctaaa actgctatggacattaacgg gttgaatatt aatactatta 23280 ccaaacttta tgaacacaat ttggttagatctatagttga tctttatgat ttaaaagaca 23340 agaaaaacca agttttaaaa ttagatctgaagattggtga taaacttttc aacaagttag 23400 ttgataacat tgaaaattca aaacaaaaaggaatggctag attactaaca ggacttggta 23460 ttaagcatgt tggtaatgta ttagctaagaatttagctaa tcattttaaa aatatcaaag 23520 cattacagca tgctagctta gagaacttaattagtttaaa tgatgtagga ataacagtag 23580 ctgaatcatt gtataactgg tttcatgaccctaaccattt gcagttaatt gaacaacttg 23640 aattaagaca agtaaaaaca gatcaattaccactgaaaat taactttgaa actaacagta 23700 tttattttca aaaacgcttt cttattaccggtagctttaa cattagtcgt gaccaaatta 23760 aggatttatt atcagctaag tttgattgccagtttgcaag tgaagtcaaa ccaacagttg 23820 actttgttat tgcaggaaac aaaccaactttaagaaaaat caatcacgcc aaagaactga 23880 acattcctat cattaatgaa gcaatttgaacatagtgatg aaaagaaaca acagttggaa 23940 aagtttatta gttagatgac tctgtatgagttttttttaa atcaaaagtt agtttaccaa 24000 tccagtcccc attttaacgg ggtatttttaacaatattgg aacactatgg ttttcaattt 24060 aaaacaattg ataaactctg aaaaagtaagcttctaatta ctagtgagtt aactgataaa 24120 atcaaacaac aattaaagtg ttattttattgaaaagatcc ctttgcccta tttgttggga 24180 acaattcaac taaggaagct tacttttaaaactaagaaag gagtttttat tcctcgaatt 24240 gatagcttag cactaattgc aagtgttaacttaaaaaaaa taaaaactgc acttgacctt 24300 tgttgtggtt caggtacttt agccattgctttaaaaaaga agtgtgatac acttgatgtt 24360 tatggtagtg atattgatat ccaagcattaaaactagcgc aacaaaatgc attaattaat 24420 aacgttagta ttaattgaat tgaagcagattgatttgatt gttttaacaa gataaaaact 24480 ccgattgatt taattgttac aaacccaccttatctgaaaa aaacacaact aaataaaaca 24540 ttaaattatg agcctaagca cagcttggtttttcaaaata aaaatagtta ttttgcatac 24600 aagcagttgt ttaatctatt actaacaaaacgatcaatta aacagttaat ttttgaatgt 24660 tctttatttc aaaaagaaag gctattaaatttgttttcaa tctttaaatc aaggccgatt 24720 tttaactttc aaaaacagtt tattggtatgaaagttgata atcaaaaact cccagtagtt 24780 gatattaaaa ataccaaaac tattaagcaacttttaaaaa tggggctagc aggaattgta 24840 aatactgata cacaaatggg attaattagttattcagagt ctactcttga caaaattaaa 24900 caacgtgcac ttaacaaaca ttatgtatcaatgtttgggt tagaagaatt aaagaagtta 24960 ccaaaaaaac tacaacaaat tgctagttacttttgaccag gtagttatac ctttattaaa 25020 aataacaaga gctacagggt tcctaaaaacttgggcttat taaacctttt taatgcaatt 25080 ggtagggttt tttgtactag tgctaatatcagtaatcaaa aaccatacac caaattaagt 25140 gattatcaaa acgatagtta ctgaataaagcaaccttgtt ttattattag aagcacttct 25200 aaagtgcaat caaataacac accttcacttgtctataatt tagatacaaa acagttggtt 25260 cgcaccacag ctaaacaaac aaaacagtttcataaattaa taactaaaca ccagttagct 25320 atctaaagaa atagaacgca aaatgaaacgttctagtcgc taattgatgt ttgttaattt 25380 acatacaaat tcatactata actttctcaattctgccctt tctcctaaaa agctagttaa 25440 tctagcaatt aatgatcagc aaaaagctgttgctattaca gatcctaatc tttttggcgc 25500 tgttgaattt tttataactt gtaagcaaaataatattaaa ccaattattg gtttaaactt 25560 aactgttgaa taccaaaaaa atgatgttaagttattacta attgctaaat caaataaagg 25620 ctttcaaacg ttgaacaaaa tagcattaattcaacaaaaa cttgaaatta attctttagt 25680 tgatcaacta acagatattg cagtaattatctgttcttta acaacatgaa aatctactta 25740 taaggatgtt tatcaagcaa aaggaattgaaataaatcaa accccgattg ccattcttgc 25800 aaatgctgtt aactgtgaaa aaactaatagcgatcaagta gttttaacag ttttgaaaca 25860 aatgaaacaa aaccaaacgg gaaaaataactacatttgat tgggatctta aacaaaaatt 25920 aaatcaaatt tcaattaatg aaaatttaaaagtaaagagt gaaattcaac cttttttaga 25980 tcaaaaaact gcacaacaat tattcagtgaaacagaactt aataatctga atgatctagt 26040 taatagatgt gaattagatt tggagcacctaaaagctgct tcactttctt taactgataa 26100 tgatgcagca gttttagaaa gtttgtgccaaaccaattta aaacagtttt tagataaaaa 26160 tcaagatcta aataaaaaag cctatcagctacgtttagag aaggaattaa atgttatcaa 26220 taaacttaat tttgctagct attttttagttgtcaatgat cttgttaatt atgcttttaa 26280 aaaggacatc ttaattggtt ctggtagaggttctgcagta ggatcattag tggctttttt 26340 attaaacatt accaagatag acccagtccaacaccagctt attttcgaac gttttatctc 26400 aacccaccgt caagatctac ctgatattgatattgatatc atggagaata aaagagcaga 26460 aatgataaat tatctgtttg aaaaatatggcaaagaaaac tgtgcacaaa ttgttacttt 26520 tcaacgtttt aaaacccgtt ctgctgttaaagaagttgct aaattattta atgattatgg 26580 cattagtgac atgatcctag gagtgttacctaaagatcaa actataacat tcactgatct 26640 taaagctact gaagatagtg ctttacaactttgtttacaa cagtttggtt taattgttga 26700 attagcacta gcaatagttg attttccaagacaatcaagt atccatgctt caggcatagt 26760 tatcgcttca aattctttga ttaaaaccattcccttgtta cagcttgaca ataatcactt 26820 tttaactcaa gtttcaatgg aatggttaagtttttttaat ctcaataagt ttgatctgct 26880 tggtttaatt aaccttacta tgattagcgatgtaattacc caaattaaac catctaacca 26940 gaccgttaac cagtttttaa ataccatttcttgaactgat caaaacacct ttataaactt 27000 agtaaatgaa gatacactag gaatctttcaacttgaatcg tttggcatga aaaaattact 27060 ggttcagatt aaacctaaaa ccattaatcaactagcaatt gttctagcgc tttacagacc 27120 aggtgcacag gataacatta acctttttattaaccgcttg cacaatggtt atgatcaatc 27180 tgacattgat cctaggattt tacccattgtgaaaaatacc tatggagttt taatttttca 27240 agagcagatc attaacatcg ttaaagttgtggctaactac tctttagaag aagcagatag 27300 cttccgtaga gccatttcta aaaaggatgttaaattgatc caaaaaaata agcgtaactt 27360 ctttgaaaga gcagttcaaa ataactttgatttaaagact actaccaaaa tttttagcta 27420 catagaacgc tttgctaact atgggtttaacctttctcat gcgttgggtt atgcactgct 27480 ttcatactga acagcttgac ttaaaactaactatcctgtt tatttttatt tatggttatt 27540 aaaccatttt caatctagta aagacaaacaaaaactaatt attagaactt tagaaaaaag 27600 tggtattgaa atttatccac ctcttttaaataaagctcaa ccaaatagtg ttatagaaaa 27660 taaaaaaatt tatttaggtc taaacctaattaagggaatt aatgacaggt acatccaaaa 27720 cttacaaaaa gtgcaacatt taattcaaactcaaaataac ttacaactaa ctgatgtagt 27780 aagttggtgt ttggataaaa ccattggtgatatcccttta aaagatttac ttttattaaa 27840 aactatgggc tgttttgatt tttttgaatacacttatgac tttaatgatg caaaggattt 27900 ttgaattaaa agcgatcacc tattgtttaccagaatgcct ttagaaaaaa aggatagtaa 27960 tttttgaatt aaacaatttt ttaccaattagacaaaatta atactttagt tgaaaaattt 28020 tcaaaaatat aatgcctgaa cttcctgaagtaactactgt tattaatgaa cttaaagaaa 28080 ctgttttaaa taaaccttta gatcaagttcaagttaacct aagaaaggtt ttgaaaaata 28140 ttgatcctca attgctgaat aaacaattaaaaaatcagtt ttttactgat attaagcgta 28200 agggtaaata tatcattttt cttttaagtaatggtttgta tttagtttcg catttacgta 28260 tggaaggtaa atactttttt gaagaaagaggtagtaaatt taatcaaaag catgttttag 28320 tagaatttca ttttgatgat ggtagtcaactcaattatca tgacaccaga caatttggaa 28380 cgttccattt gtatgaaaag ttagaacaagcagcacaatt aaataaactt gcatttgatc 28440 ctctagaagc tggttttgac tataggaaaatcttccaaaa agcacaaaat tcaaaacgta 28500 aagttaaaac ttttatttta gaccaaacagtgattagtgg aattggcaat atttatgcag 28560 atgaaatctt atttgcaagc aaaattaatcctgaaacaat ggttgatcaa ctaacaatta 28620 aagagataga gattttatgt aaaaatgctaccaaaatttt agctaaagca atagttatga 28680 aaggtactac catcagcagc tttagttttaaaaaagatca tactggaggc tatcaaaact 28740 ttttaaaagt tcacactaaa aaagatcaaccttgctcagt ttgtaaccaa ttaattgtta 28800 aaaagaagat taatggaagg gggagctatttttgtttaaa ctgtcaaaaa atcacaacca 28860 aagtttctac aaaactcaat ccataatttttatttttttg cacttattta taaggtgtaa 28920 tgaaagatgg ctcaaaaaga aataattaataagaaaaata ctcaaaaaaa tagtagtttt 28980 attgaaagta ataatttgac aagttttgatttttttgatg caaagaaaaa cagtgaaatt 29040 gaaacaattt caactggaag tttaaatttagatgaagcat tagggtctgg tggtctacct 29100 ttaggtagga tagtagaact atatggaaatgaatcatctg gaaaaacaac tattgcacta 29160 aatgcagtcg ctagttttca gaaagcaggtaaaacagcat gttatattga tgctgaaggt 29220 gcacttgatt tagcatatgc taaatcaattggtattgatc taaataaact tttgattgct 29280 catcctaggc atggtgaaaa cgcttttgctcttatcgaat cattaattaa aacaaacaag 29340 atatctttaa ttgttattga ctctgtagcagcgttaattc ctaaacaaga gttagaaggc 29400 acaattgaag aacaaactat tggcttgcatgcaagaatga tgtcaaaagg tttgcgaaga 29460 atacaatcga tattaccaga ttctaaaacttgtgttttat tcattaatca gttacgcgaa 29520 aaaccaggag tgatgtttgg aaataacgaagttacaacag gaggaaaagc tctaagattt 29580 tatagttcat taagaatgga agctaagcgtgttgaattac ttaaggataa attcaacaat 29640 tatgttggca taaaaacaaa agtaatggtatctaaaaata agattgctaa accttttggt 29700 gttgctatat tagaaatcat gtttaaccgtggttttgtac atgaacatga agttattgac 29760 ttagcactta aatttaatgt tgttgtaagagctggaaatt cttattcttt taacaatgaa 29820 agcattgctg ttggtaaaga aaaattattaaatgttttat cagaaaagcc agcattattt 29880 gaacaaataa aagaactaac tgttcaacaattggctaata aaaattcatt tcaacaaaca 29940 gctagctaac atgagagttt caatttaaccaaaaagacaa gcatatagaa tgcactgtca 30000 aagacaattt tggtcgtgag aaactaataaatttgatttt tcaaattggt gatgctattg 30060 aaacttatca tactacttta ataagattcaaaattcccaa gcattgtttg aatgcaaggg 30120 atcaaatcaa aaaaataatg gagggcaaataaaaatgatt acatctatct ttggaaaagt 30180 tacttttgta ggcaaaagaa aaataattgttgagcacaac tggatttcat attgatttaa 30240 tacaaaagaa aaccataaat ttgaaaaaaatttggaaaaa aataagcaaa ttttttgtca 30300 tattattaaa aaaattgtcg ctaaccaaattatagaagag gcttttgcct ttaatactct 30360 agaagaaaaa gagtggttct gtagattaatagaactcaat ggtattggta gtaaaactgc 30420 acttaatttg ctcaataatg accttgaggaaattaaacaa tacattctgg aaaataacta 30480 cagtgcatta tgtggtatta acggtgtaaataacaaaata gctcgtgcac ttttatcact 30540 tgaaatattt gaaaaatctg aaaataataaaaatattaaa ggagttcaag ttgctgatgg 30600 ttatgatgaa ttgtttgaaa cactaaagtcacttggttac aaacaacaag aaattcagga 30660 tgcactaaaa atgatagaag taaaacctgattttgatata agtcagttag ttgcagaagt 30720 aattaaatta atgtctttta agaataatgaaattacaaat aaaaccgcct aatacctttg 30780 atgaatttgt aggaaaacaa gaaataattagtcaaattca attaagtatt aaagcatcta 30840 aattaaataa aacacaacta gatcatatcttgttatatgg cccacctggt gtgggtaaaa 30900 ctactttagc cagattaata gcaaatgaattgaaaacaaa gttgcaaatt attcaaggtg 30960 gacatttaca aaaaccaagc gatttcttaaacgcaatttc actcattaaa aaaggtgatg 31020 ttctttttat agatgagatc catgccgtagcacctaatgt catggaacta atgtatccag 31080 ttatggatgt gttcaaaata caagtattaattggcaagga ttttaattcc aagatagttg 31140 aaatgaaggt aaatcctttt actctaattggtgcaactac acaacttggt aaaatcatca 31200 atcctttaga agatagattt ggcgttatcttaaacattaa ctattattca aatgctgaaa 31260 ttgaaaagat ggtaagtatc tatggaaagcaaatgaagtt agagctaaat tcaaatgaaa 31320 tttcagctat cactgaacat agtaaacaaacaccaagaat tgcaattaga atagttagaa 31380 gaatatttga acaaaaaatt gttaataaaaaaatagacct tgagggtttg tttaagaatt 31440 taatgattta taaaaatggt ctgcaaagtattgatgtcca atatcttgag gttttaaatc 31500 gccaaaatga accacaagga attaagtcaattagttccat gttaggtata gacagacaca 31560 ctatagaaaa taaaattgaa ccttttttgttgcgtgaaaa tatgattcaa aaaaccaaaa 31620 aaggcaggat tattacaaat agcggaagagaatatttagt taacttttaa gataaaaaac 31680 attactttaa attatattta atgatgcaaaatgtctttta tcataacagt aataggtgct 31740 gggcatgctg gattggaagc cgctttcattgtaagcaaat tcaacatcaa agtaaacctt 31800 ttagttcttg atataaatca tttaggttcttgtccatgta atccttcaat tggtggacct 31860 gctaagggaa ttgttactag ggaaattgatgttttaggag gtatgcaagc aattgctgct 31920 gataacaatg ccttacaata taaattactaaatagttcaa aaggacctgc tgtgcaagct 31980 atcagagcac aaattgacaa aataggttataaaaactggt ttcaaagtca agttaaatta 32040 aataaaaaca ttaatctaat tcaatctgaagcaatcaatt taattgttag aaatgaaaaa 32100 ataaaaggcg ttattttaaa agacggaagtgaacttttaa gtgatgcggt tattatcact 32160 accggaacgt acctaagatc aaaaacatactgtggtaata cagttaaaaa tcaaggacct 32220 gatcaatcta aaaatagtga aaaattaagcacaaacttaa ttaacagagg ttttaaaaca 32280 attcgtttaa aaacaggaac tccgccaagaattttaaaaa cttcacttga ctataatcaa 32340 atggaattag aaattaataa taatcaaaaccttgctttta gtactacaaa taaaaatttc 32400 ttaccacttg aaaaacaaat accttgttacttagttcata ccaatcaaaa aattcacgat 32460 ctaatcctta aaaacttaaa aaaatctgcaatgtttaatg gtagtatttc agcacaagga 32520 ccactttatt gtccaagcat tgaagacaaagtttttaagt tctctcaaaa acctcgtcac 32580 caaatttttg tagaacctga atcattgagtctagatacta tttatttagc aggattatca 32640 acttctttta caccagaaat tcaaaaagaaatcatccagc ttttacctgg ttttcaaaat 32700 gcagaaatta aaaagtttgg ttacgctattgaatatgatg cttttctatc taatcaacta 32760 aaaccaacac ttgaaacgaa gttaatagaaaacttgtatt ttgctggaca aattaatggc 32820 actagcggtt atgaagaagc tgctggtcaaggtttgatgg caggaattaa tgctgcttta 32880 aaattattaa aaaaaccacc atttattttgcaacgtaatg aggcttatat tggggttatg 32940 attaatgatt tagttactaa aacaatcagtgatccatacc gtttgttaac atccagagca 33000 gaatatagac tatgattgag aaatgacaatgttcaagaac ggctcattaa aaaaagcttt 33060 gaacttggtt taacagataa aaaaacatatgaattgttcc ttaaaaagga aaagaaaaaa 33120 caggaattaa tttcattttt aaaaaacactcaagtaggca aggttaaagc attgaaattc 33180 actaataaaa ataccgctca atcactttatgacttcaaca aacgaagtga aataaattta 33240 gataaattga tcaaagatct tcctgaaaaataccaattag attcagaaac acttaaacaa 33300 attgaaattg aaattaaata tgagggttacataaagaaaa atgaaaagta ttttaagggt 33360 ttagataaat taagcaaaat taaaattcctcatacttttg attaccataa ggttaagaat 33420 ttagctagtg aagctatttt taaactatctaactttaagc ctagtaattt agcaattgca 33480 agtcaaatag ctggagtgaa ctttaatgacattatagcca taaaacattt tttaaaaact 33540 tatgaataac ctaataataa gttagttaaaaatttttcaa ttaaaaacat tgactttgaa 33600 accggaatga aaaaataatg attttataagggttaaaggt gctagagaaa ataaccttaa 33660 aaacattaac attgatatcc ctaaaaatcaatttgttgtt attactggtc tatcaggatc 33720 aggtaaatct tccttagcat ttaacacaatttatgctgag gggagaagaa gatatttaga 33780 gtctctatct tcttatgcac gccaatttttaggtaacagt gataaacctg atgttgatct 33840 tatagaagga ttatcaccag caatttccattgatcaaaaa accacttcac ataacccacg 33900 ttcaactgtg ggtacagtaa ctgagatctatgattatcta agacttttat gagctagaat 33960 tgggacccct tattgtccta atggtcatggttctattcaa acgcaaacaa ttaaccaaat 34020 tgctaatcag atttttgatt tacctaataaatcaaaggtg caattattag cacctactgt 34080 taaaaatcag cgcggcattt ttacaaatgaatttattaaa tacaagcaat taggttttct 34140 tagagtctta gttgatggcc agatttacaccttagatgat gaaattaaac ttgataaaaa 34200 tactaaacac aacattagtg tagtgatcgatagaattatc atcaataaag ataatcaaac 34260 ttattcaagg atagttgata gcattgaaaccattgatagg ttaactaatg gcaagataga 34320 agttcttaag gaagatggaa caatattaaatttcagcaaa aatcatggtt gtgataaatg 34380 tggtttttct attagtgaat tggaaccaagattattttcc tttaactccc ctttaggttc 34440 atgttcatat tgcaaaggac ttggttttagttatgaacct gatgtagaca agataattgc 34500 tgattctaaa ctttctatta accaaggagccattgatatt tttaaaaata ttgtgcatgg 34560 aacttctttg gattgacagc gctttttatctttagttaat cactataaaa ttccattaga 34620 taaaccaatt gaacagttag ataagtcacaacttaattta attttagaag gaagtgatga 34680 acctattgaa ataaaaacaa tttccaattcaggtgctaag aatatccgct ttgagcatta 34740 tgaagggata gctaatttaa ttaaaagaagacacctagaa acaaacagcc aagtaagtag 34800 agaatgatat tctgcataca tgtctgaaataacatgtaaa aagtgtcatg gaaaaaaatt 34860 aataaaagac gctttaagtg ttaagttaggaggaattgac attattagct ttactgaact 34920 ttccattgat aaaagtattg attttctattaaaactagag ttaaatgatg agcaaaagaa 34980 gatcggtgaa ttagctttaa aagagattattaatcgtctt tcttttctta aaaatgttgg 35040 tttagattat cttaatcttg caagaagagcttctacgctg tcaggtggag aagcacaaag 35100 aattagatta gctacccaaa ttggttctcaacttactggt gttttatatg taatggatga 35160 accttctatt ggattgcatc aaaaagacaatatgcgttta attaaaacaa tgatggtaat 35220 gcgtgattta ggtaacacct tattagtagttgagcatgac agtgaaacaa tgttagcggc 35280 agattattta attgatattg gtcctaaagcaggtaatgaa ggtggtgaat tagttgcttg 35340 cggtacacct ttacaagtaa tggaaaactcaaactcaatt actggacaat atcttagtgg 35400 taaaaaacaa atctccattc caaaaaatagacatagtggt aatggtaaaa caattattat 35460 caagggtgct aaagttaata atttgaaaaatattaatgtc accattcctt taaataaatt 35520 ggttttgata acaggggttt caggttctggaaaatcctct ttaattaatc aaacattagt 35580 tccagcttta gaaagaattc tttatcgtaaaggtgttaaa aaagatacat ataaggaaat 35640 aattggtgct aacaacattg ataagataattgttgtctct caagacccaa ttggtagaac 35700 accacgttct aatcctgcaa cctatattagtgtttttgat gatattcgtg atttatttgc 35760 caacacaaaa gaagctaaag caagaggatatacaaattca cgattttctt ttaatgttcc 35820 aggtggtagg tgtgataagt gttttggtgatggtgtgatt cgcattgaaa tgcatttttt 35880 acctgatgtt tatgtcaaat gtgaagtatgtaatggcaag aagtacaatt cacaaacact 35940 ggaaattaaa tatttgggaa aatcaatttttgatgtttta caaatgtctt gtaaagaagc 36000 ttatgaattt tttaaagcta tcccaaatatatcacgtaaa ctaaggttgt tatgtgatgt 36060 tggtttagaa tatttgcaat taggtattaatgtcactttt ctttcaggtg gggaagcaca 36120 gagaattaag ttatctaagt ttttacaaaaaaaatctact ggtaaaactt tgtttgtttt 36180 agatgaaccc tctactggct tacatttagaagatataaac aaactattaa caataattca 36240 aagaatcatt aagaatggtg atacagtagttgttatagaa cataacttag atattattaa 36300 ggttgctgac tatatcattg atttaggtcctgaaggtggt gacaatggtg gtcaaattgt 36360 tgctcaagga acacctgaac aacttataaaccaagttaat aaatcttata ctgcccaata 36420 tttgtccaaa attttaaaac cagattcaatttaaaaatta tgcaccaagt tttttatcaa 36480 aaatatcggc caatcaattt caaacaaaccctaggacaag aatcgataag aaaaatcttg 36540 gtgaatgcta ttaacaggga taaactacctaatggttata tcttttcagg tgaaagagga 36600 acaggtaaaa ctacttttgc aaagataatagcaaaagcga taaactgctt aaattgagat 36660 caaattgatg tttgtaatag ttgtgatgtgtgtaaaagta ttaacactaa tagtgccatt 36720 gatatagttg agatagatgc agcttctaaaaatggtatta atgatattag agagttggta 36780 gaaaatgttt tcaatcatcc cttcacatttaaaaaaaagg tttatatttt agatgaagca 36840 cacatgttaa ccacccaatc atggggtggcttgttaaaaa ctttagaaga atcaccacct 36900 tatgttcttt ttatttttac aactactgaatttaacaaga ttccattaac aattttgtcc 36960 agatgtcaaa gcttcttttt taaaaaaataactagtgatt taatccttga aagattaaat 37020 gatatagcaa aaaaagaaaa gattaagatagagaaagatg cattaataaa aattgctgat 37080 ttatcccaag gttcattgcg tgatgggcttagcttactag atcaattagc aatttctctg 37140 atagtgaaaa aattagtatt actgatgttgaaaaaacatt taatatcgtt gatagaaatg 37200 caaaatttac ttttattaaa gcagttttatcaggagatat aagaatttta actatcattc 37260 ttgacaatgt tatagaagaa taatggaacaatttaatgcc tttaaatctc tattaaaaaa 37320 gcattatgaa aaaacaatag gttttcatgataaatacatt aaagacatta atcgtttcgt 37380 atttaaaaat aatgttcttt taattcttttagaaaatgaa tttgctcgta attccttaaa 37440 tgataattct gaaattattc atttagctgaaagtttgtat gaaggaatta aaagtgttaa 37500 ttttgttaat gagcaagatt tcttttttaacttagcaaaa ttagaagaaa atagtcgtga 37560 tactctttat caaaattctg gattgagtaaaaactatact tttcaaaact ttgtaattag 37620 tgaaggaaat aaaagagctt atgaagcaggcgttagatta gctgaaactc aagataacga 37680 attttcaccg ctttttattt acggagaaaccggtcttggt aaaactcacc tactacaagc 37740 aataggaaat gaaaaatttc gtaattttccaaatgccaga gtaaagtatg ttgtttcaag 37800 tgattttgcc caagaagttg ttgatgctttttatcaaagg gataaaggta tagaaaaact 37860 aaaaaaaaat tatgaaaatt tagatttagttttaatagat gacactcaaa tatttggcag 37920 aaaagaaaaa accttagaaa ttcttttcaatatttttaat aacctagttc taaataaaaa 37980 acaaattgtt ttagtttctg ataaggctcctgatgaacta attgatattg atgcaagaat 38040 gatttctcgc tttaaatcag gattattactaaagatagaa aagcataatt tgtcttcact 38100 ttgtgaaata cttactgtta aattaaaagaaaaagatcct aacatccaaa taactaatga 38160 ggcaagacat gatgcagcac aaatttcaggtaacgatgtg cgtgctttaa atggaattgc 38220 aacaaagtta ttattttttg ctaaaacttcaaaacaaaat ttaataaata ctgaaaattt 38280 aaaagaaatt ctttttgaag aatttgagaagtttcataaa aagagctttg atccttattt 38340 attaatagag aacgtttgcc gtagatttaatgttcctatg gacagtgtac tttcagaaaa 38400 tcgtaaagca gaacttgtcc gtgttcgtgatgtgtgtaat taccttttgc gtcaaaagta 38460 caacatgcaa tttcaacaaa ttggcaaaatatttaagaga agtcattcaa gtgtattaat 38520 ggcagttaaa agagttgcta aaatgattgaaaatgacagt tcattacggg atgtaattac 38580 atcattagta atttag 38596 2 22684DNA M. genitalium 2 ttaattaata aaaaacaacg cggaaaagct ttaaatttatgcaagctagt gaattaacac 60 caaagtggta tgtagctcct gttagtatta aagatgaagctgttgtaaaa aatctaaaag 120 ctaaaattca agctttagga tttaatcatg agattgttgatgttaaagtt ctaaaagaaa 180 gggaagttca tgaagaagtt tattcattaa aatcaggaaaacttcctcgt tccttaaaga 240 acactacttt taacaaatgg tttgttcttg atgattaccgttatcttagg gtaaaaatta 300 gtgaaaaaaa tctccttggt agatacatct acataaagatgatttatagt gaagatgctt 360 gaagaattgt tcgtaacttc cctgggatca ctggcatagtaggttcttct ggcaggggtg 420 ctttacctat ccctttagat gaaaaagatg ctaataatttagaacaaatg cttaaaggga 480 tatcaatcaa tcctagcaaa cgaattatgc taacaaatactgccattatt gaaatggaca 540 gtgataaatt tgatgaaaaa tttcaatata tcttaaaacaaaaacaagcc attcaaaaac 600 caaaagagga tgaagattca gaaattgttg atgctgaaaaactaaaagaa gcttttaaaa 660 aactacaaaa tagtcaagaa caagatgaat ggaaagaaaaagcaacgatt attcaaagtg 720 agcaaaccaa acttgatcca tcagtattag ttccttttttgggcaaatat gaaattcttg 780 atactgacaa taaagttgaa caactctttg aatttagtgttggtaattta gtagaggtac 840 atttaactga tactattcat gttcaaggac agataaaagcactttatcaa ggtacagtta 900 acaaagcagt tgtagagata gaattaacat ctaaaacccaattaattaac ttacctttag 960 aaaatttaag ctttgttgag tttgagtaat aattcttgggttgatattta gttttgcacc 1020 aagataacaa tgaaggtttt aactgaactc caaaagcagatatttaccat tgtcaaaaag 1080 gaaaatggta aacctattcc ccctggaata gtggtaagaatgatggaaaa tagtcctaat 1140 tttccaggta aacatctcat ctatcgggcc attgatgatctgcttgattg agccatctta 1200 aggaaagctg gtggggttac aaaccagcta ttagttaactatgaacctgc tgagccttta 1260 cttgataaaa aactacaagg gattttaacc ttaggaaataagaatagtgg ttttatccgc 1320 tctttggatg atgataaaac tgtgtattat gtccattactctaatttaac tggagcttta 1380 gatggggatc ttgtggagtt ttgtaaatta gataaaccccaatttggtga taagtttgat 1440 gctgcagtta ttactattct aaaaagagca agaatcttgtatgcaggtaa ttttttagta 1500 gatcaaaatg agtttgcctt ggaatacaaa attgttgctgataaccctag attttattta 1560 actatgattg taaatcctga ttctatccca aataacttagcatctaacac caagatagct 1620 tttcaaattg atgagtatga tcctgataac aacttatgtaaggtttctgt acaacaagtt 1680 ttgggtaaca atgatgatcc gctaattaat ataaaagcaatcatgttgga caattccatt 1740 gtctttgaaa ctaacgatgt agttgaacag catgctaacaagttaagttt tgatactgaa 1800 gaacaacata aagcttaccg tcaggattta actgatttagcttttgtgac tgttgatcct 1860 acaacatcaa aagaccttga tgatgctatt tatgtcaaaacaataccaac aggttttgtg 1920 ctttatgtag ctattgctga tgttgcacac tatgttaatagaaatagtga aatagacatt 1980 gaagcaaaac acaaaacaag ctcaatctat ctacctggtcattatgttgt gcccatgcta 2040 cctgagcaat tgtcaaatca gctctgttct ttaaatccagcacaaaaacg ttatgttgtt 2100 gtttgtgaga ttagttttga taatcaggga aggattaaaacaaacaagct ttacccagca 2160 acaattattt ccaaaaatcg ttttagctat gatcaggttaacaagtggtt aaataataaa 2220 tcagaattaa actgtgatga aacagttatc aacagcttaaaagcagcttt tacactaagt 2280 gatctaattc aagcgcaacg tcaaaaacgc ggtacaattgatctttcaca caaagaaact 2340 gagatagttg ttgatgaaca ttattttccc attaagataaattttttggt tcacgataaa 2400 gctgaaacca tgattgaaaa tctcatggta gtggccaatgagacagttgc ttgggtgtta 2460 actaacaaca aaattgcttt accatacaga gttcacccaagaccaagcaa aaagaagtta 2520 caaagtttga ttgaaacagt tggtgagttg aacataactaaaccccaatt taacttagat 2580 actgtcactt caagccaaat agctagctga ttaaatgaaaacaaagataa tcctagttat 2640 gagatctttg taatcctctt attaagaaca ctaggcaaagctttttatag tgttaatccc 2700 ctgatgcact tcagcattgg ttctaaccac tatacccactttacttcacc gattagaagg 2760 tatatagatc taaccattca caggttgttg tgaatgcatctttttactcc cgatcaattc 2820 actgataatg aaagagatca actcaaacaa gagttggaaaaaattgctga tacagttaat 2880 gatacagaga ttaaaattat caattgtgaa agaaatgccaatgattatct aacaacgctg 2940 ttattatcaa aacaaattgg caaaaccttc agcggatttatttcagcaat tactagcttt 3000 ggaattttta tgagaatgga tgaaaataac tttgatgggttaatcaaaat tacaactatc 3060 cctgatgatt tctttatttt tgaaaaggaa aaaatggtattgaaaggaag aaaaactaat 3120 aaggtttata aaattggcga tcgtttggaa gctaaactaagtgagattga tttcatccaa 3180 aaacgtgcta ttttaacact catataatta gcagtgcatcaaaaccagca tgaagaaata 3240 taattagatg aagataactt tcatttctgg acaagaagtgtcgttaggca cttctttttt 3300 attgttttca aaaaaaatag ttatgaatga attaaaccaacccttacttg ctattattaa 3360 aaatgttgct aaaaccaaaa acctttctat agaagaggtggttttttgtt tgaaaacagc 3420 tttagaacaa gcctataaaa aacaccttaa ctttgttaatgttgaagtta acattaactt 3480 tgataagggg attattaatg ttgaacaact ctttaatgttgttagtgatg aaaatgaaga 3540 ttatgatgac tttcttgaaa tccctttaca agcagctaacaaaataaaca gttcattgca 3600 attaggtgat gtgttgcgaa aaccaatccc cttaaaaaacattagtagtg atcttatcaa 3660 taagatgatt gctatcttta accaaaagat tagtgaaacaaactttaaag cagtaatgag 3720 tgagtttagt agtgaggttg gggaagtgat tgaagcgaaagttgaagata ttgatactaa 3780 caaagaaggt ggtttaaagg gttatattat taaccttgaaactacaaagg gttatatctc 3840 caagcgggaa ttgtcaaaag gggagcgctt agagataggtaaaaaatacc tctttgttat 3900 caaagaaatc caacggcaag catcgttatg accaattactttatcaagaa gtgatacccg 3960 cttactacag tttttgttaa cttcaaatac tccagaaattgaaaatggta cgattgtaat 4020 caaaaagatt gaacgttccc caggagtgaa atcaaagatagcagttatct ccaatgatcc 4080 tgcagttgac ccagttgctg ctatcttagg acctaagggtgagaagatta gggggattag 4140 tgaggaattt aatggtgaga ttattgacat tgtcttttggaatgaagaca agttaaagtt 4200 cttaattaat gccattttac ctgcagaagt cattggttataacatcttgc aggatgatga 4260 gcgtgatact agtattgaag ttgttgtacc tgcaaaccaaattgctaatg tttttggttt 4320 taaaggtgta aacattaggt taattagtaa tttaacaggttgaaatagtg ttgatgttta 4380 cagtgaaaaa gatgcaagtg aagccaacat taaattcacgaggttaagct ttgaacctga 4440 agggttgttt ggcatcaaaa aaagaaggga aaagatcattagtaatgatg ctactgataa 4500 agtcttttac acctctaaag acaatgtgat agatgatgagattattgttg atttagctaa 4560 agatctaatg gttgataata aacaaaaaca acctgagcaagttgcaaagc aagttgttga 4620 aaaatcacaa ttagaaaaac aagttactcc aaaagaaaaagagaaagttc aaccaaaagc 4680 taaggttcat tctaatagcc attccaaaaa accagctaaacctaatcaga ttttttctat 4740 cactgttgat gctagtgata agaatcttaa aaaagatcaagttgataata accaaacaaa 4800 cccccaaaca aaacaaacat ttgatagctt tgatgatctttaacattatt aagaaataaa 4860 ccaattagtg atctataaaa acaatggaaa aatttttaaagtacgaaatt aaggttaaca 4920 acaaccaacc aaccaacact aaccctaact atgggatctttgaagtagca ccgttagaat 4980 caggatttgg gattaccatt ggtaatgcga tgcgccgagtgttacttagt tgtatcccag 5040 gcgctagtgt gtttgccatt gccattagtg gggtaaaacaagagtttagt aatgtggagg 5100 gtgtgttgga agatgtgact gaaatggtgt taaacttcaagcaactagtg gtgagaatct 5160 ctgatctttt gtttgaagat ggggagatga tcgaaccacccttagaaagg tgaccagttt 5220 taaaagttac tgctgaaaaa aagggtgcag tatatgcaaaggatcttgag tgtccagctg 5280 gttttgaagt gattaataag gacctttatc tcttctctttacaaaaggac atgaaactaa 5340 cagtcagtgt ttatgttaaa cagggtaggg gctttactagctttcttgaa aacagagaat 5400 tgatcaattc gcttggcatt attgctacag atgctaacttttccccggtt ttacactgtg 5460 gttatgaagt tcaagaggtg aaaacttcca aacaaaagttaactgaccat ctcaccttta 5520 agattgctac taacggtgca attaaagcag tggatgcgtttgctatggca gcaaagatcc 5580 taattgaaca cttaaaccca attgtaagtg tcaatgagtcaattaagaat ttaacaatta 5640 tccaagagaa agcagaggaa agaaaggtga aatcatttgccaagcaaatt gaagaacttg 5700 actttactgt tagaaccttt aactgtttga aaagaagtgggatccacaca ctccaagagt 5760 tactatcaaa gtcattaact gacattagag agattagaaacctaggtaag aaatcagaac 5820 gggagattat caaaaaggtg caagagttag gtttaaaattccgttcttaa tttattaaaa 5880 aaccattagc acaaaagatt aaaacttact atgaaacagtgttttgttgt tacaactacc 5940 aaacgcttag atagtctttt agctagctta ctgaacctttcaagagtaaa ggtagtgaag 6000 ctgatcatga atggacagat taaagttaat gaaaaactaacttttaaaaa cagtttaata 6060 gttgcaaaag atgatgtaat taaagttgag attcatgatgagacaactag tgatttcatt 6120 actagtgttg aaccttataa cttaaagctt gaggttctttttgaagacaa ggatttgatg 6180 gttattaaca aaccatcagg tttgttaacc catcccaccactttcaatga aaaagccagc 6240 ttgttagctg cttgtatctt tcacaacaac aaaaaccctgtttacttagt gcacagattg 6300 gaccgtgata ctagtggggc aattgttgtc tgtaaaaaccaagcaagctt attaaatttg 6360 caaaatcaac tgcaaaatcg caccttaaaa cgttattatgtagcactagt ccacttccct 6420 tttaatgcct taactggttc aattaatgca cctttagcaagggttaataa caacaaggta 6480 atgtttaaaa tagcccaaac tgctaaagca aagcaagcaataactaagtt taaagtgatt 6540 aatcagaatg aaaaagcagc actaattagc ttggaattgttaacaggtag aacccaccaa 6600 attagagtgc atctgaaatt tatccaacat ccagtttataatgatccact gtatggaatt 6660 aaaagtgaaa agaaagatag ctatggtcag tttctccatgcaaacaggat ctgttttatc 6720 catcccactt taaacaaacc tatggacttt cacgccccacttgaacctaa gttttcaacg 6780 aaacttaaga gtttaaactt atctttaacc gatccactccatgttctttt taagtaactt 6840 aagataattg aaacattaaa taagataatt acaagctatatgtccactga caaaaaaacg 6900 ctaggcgaaa aacccaattc aaccaaacca gaactatctgaagaattaat tgctgaactt 6960 aaaaaacagc gtattcttga aaagaatcgt ccttacaaaaagatgattta tgttgacaat 7020 aaagtgcaac gcaaacaccg tcatgaaaac atcgcttttctcaaaaccct tcatgaaaat 7080 aaggagagtg atgttcctaa aaaaagaagg ggtagaaaacctaaacacgc tcctttaaaa 7140 gaaaaaaata atctgaagtt atttgatatc ttagaaggatcgttaaaaag ccacattgaa 7200 aatgatgaca ccaacacagt catcaacctt ctaacagaagcttgagaaaa gaaaagcaaa 7260 aagaaacaaa aaaacatcac gctttcaaat aaggaaattattagtgttct cgctaagttt 7320 gaactacctg aagatgaaat tatctatgtt ttggatgaactacgtgataa ggggattcaa 7380 ctccaacacg atgttgaaga gcacatccat gaatttcgtgctaaccaaga cctttcaatt 7440 attgatgaag atattgaaga gttaacaagt aagaacatctctaaccgtga taaggttgat 7500 gataatgtta ggttcttttt aggatcactt gacttttctaaaatgttaga ttttgaatct 7560 gaacagcgga ttgccaaggt tttaaatagt actgatgaagagtcacgtaa gtatgcaatt 7620 aatcagttgg ttacttcaaa cttaagacta gttgtttctattgccaaaaa acacctagaa 7680 agagggttgg attttaatga tttaattcaa gagggtaatttggggctttt aaaagctatt 7740 tccaaattta actgatcttt agggaataag ttttcaacttatgctacttg atggattaaa 7800 caagcaatta caagagcaat agctgatcaa gcaagaacagtaaggatccc tgttcatatg 7860 gtagaaacca ttaaccgctt agctaaagca gaacgggctttgtatcaaga gttagggcga 7920 gaacctactg atgaggagtt agctgaaaag atgggaggacaagctgaagg atttaatgtt 7980 aaaaagattg ctgaaattaa acggttaagt ttagatccagtttcgcttga taaaacagtt 8040 ggacatgatg aagagtccca gtttggtgat tttgttaaagacacagacgc tcaaactcct 8100 gacgagttta ccgaaagccg ttcaaattca gaaaaaattgatgaattgtt gaacaataat 8160 ctttctgaac aagaagagtt aattgttaga atgcggattggcatgccccc ttacaatgaa 8220 cctaaaacac ttgatgaagt aggtcaaaag attttgatccctagagagaa gatcagacaa 8280 attgaaaaca aagcaattag aaaattgaga catgcagttagaaacaatcc tattagtatg 8340 tcatttctaa gaattaatga aaaaaaggat tagactatttttaataactt aaattttata 8400 taaatattaa gtaatggcaa ccattcagga aatcgagtgtgattttttag ctaaaatagc 8460 acaaaaattt actaatgcag agattgaatt aattaacaaagcattctatc acgctaaaac 8520 ttggcatgaa aaccagaaac ggcttagcgg tgaacctttttttatccatc ctttaagaac 8580 ggcattatca ctagttgaat ggaacatgga tcctatcactatttgtgctg gtttgttaca 8640 tgacatcatt gaagatacag accaaaccga agctaatatagcaatgattt ttagcaaaga 8700 aattgctgag cttgtcacta aggttacaaa gattaccaatgaatctaaaa agcaacgtca 8760 tctcaaaaat aaaaaggaga atcttaactt aaaaagctttgttaacattg caatcaattc 8820 tcaacaagag ataaatgtaa tggtactaaa actagcagatcgacttgata acatcgcttc 8880 cattgagttt ctccccattg aaaagcaaaa ggtaattgcaaaagaaactt tagaacttta 8940 tgcaaagatt gctgggagga ttgggatgta tcctgttaaaacaaaattag cagatctttc 9000 atttaaggtg ttggatttaa aaaactatga taacaccctgtcaaagatta acaagcaaaa 9060 ggtcttttat gacaatgagt gggataactt caaacaacaattaaaaaaaa tcttagcgca 9120 aaatcagata gaataccaac ttgaaagtcg gattaaaggcatttactcta catataaaaa 9180 actaactgtt catgaacaga acatcagtaa gatccatgatctttttgcta tccgcttaat 9240 tactaaatca gaacttgatt gttatcacat ccttggtttaattcacctta attttttaat 9300 tgacagtaaa tacttcaaag actatattgc ctcacctaaacaaaaccttt accaatcaat 9360 tcataccact gttcgtttaa aagggttaaa tgttgagatccaaattagaa cccaacagat 9420 ggacaatgtt agtaagtttg gcttagctag tcactggatctacaaagaac agaaagaggg 9480 attgttagca cctgctttgc aacttaatta cctagtgacaaaacaaaaac actcacatga 9540 ttttctaaaa aggatttttg ggactgatat tatcaagattaatgttagtg ctagtcatga 9600 acctaatgta attaagcaaa ttaatgttga tagcaacaataaactccttg atattgcttt 9660 tgaaaactat cccaagcaat ttgctaaatt aaccaaaattgaaattgatg gggttgagat 9720 caattctttt gatactagtg ttgaaaatga gatgctgattgaattttact ttggcaagaa 9780 taacaatttg aaatcaaagt gaattaggta tatgaataaccctatatacc gtgaaaaggt 9840 aaaaaagagc ttggctaaac tagctaaatc tggtagatacagtgagttag ctttttatga 9900 aaaagaactg ggtgaaaaac agttaaaact tgctagtgaaactgaaatcc aaaaacgctt 9960 aaacacccta agaattaaaa aaatgagtga ttacttagcgttaattgagt gtactaactt 10020 tactaatgat gaacatttgt tgtttctagc taaaaacaacgacaagtgaa ataaactaac 10080 aaaaccactt aagtttgctt tttcaaaagt agtttttcacaactcttact ttgaacaaat 10140 tgaaggtatt tttatcacca aaatagtgat tgaaccatgttgtagtaaga tccctgatat 10200 gcctgaacaa gtaactggta tcttaactaa aaacattttaagtgttcacc gttatggttg 10260 taagaattta caaaataaaa agcagttaaa aattatcccgttatattgaa atatccagca 10320 gttaaaacta aaaccacgta agtttcgcag ttacattaacattaacggag tgtggagtga 10380 aaaaaccatt aataaaatct gtcaaacaat tattaatggtgatggttata ttgaaaaaat 10440 aattcccaag atcaacaaac aaaaagatga atttgatttaaacatcaccc tttttgttaa 10500 taactaccaa caacttctca ccttaatgga ccaaattaccactaagaata tcagctttag 10560 ttgaaaatac ctttagagtg gctttttaat gttttgatccgcttttcacc ccacaaatgt 10620 cacaaaaatc taatttcttt caaaaacgtt attcccctacagctaccaga aggtattatg 10680 gcaaaattga gaccaatttt atccaaccaa atttagctgatattcagatt aaaagctacc 10740 aaaaattctt agatcatgat cttgaaaaat taattgcctcatattttcca atcaaatccc 10800 ctaatgatcg ctacactatc aattttaggg gattacacagaactgaacca gaacgtgatg 10860 aagcacaatc acgtgctcaa tctaaaactt atgaagttggtatttatgct gatcttgaat 10920 tagttgataa tgataaagga acagttaaaa aagcacggaaatcaaagaaa aatattgcta 10980 gcaatacaaa tggtgtattt ttagctagca tgcctttaataacccatgat ggggttttta 11040 ttatcaatgg gatagaaaag tttgttattt cccaaataacccgttctcca gggatataca 11100 tgctaacaaa atcccaacta aaactatcca actcccgtaaaagagtacag gaaggttatg 11160 tttgtgaggt tttacctgct aatggttcag tgatgcttatatacatctcc aataaaaaaa 11220 agattgaaga tgcttttgta caaattcttt taagagatgcggtaagagaa ggtgctaaga 11280 ttttccctat tacaacactt ttaaaagcgt ttggtttaaataatcgtgag atccttaaaa 11340 tctttaaaaa caatgaattt atcaaacgtt cattggaagcggaaatttac aatgctaagg 11400 attttttaag caatgttgat cctgaaatca aaaaccttttaaaagaattt agagatggta 11460 aaactgattt aagaagaaaa gggatcgctt ctgatcagaaattaagatca cttgttaatg 11520 aatatgtaac gcttgagaaa caatataatg cgctaaaacaaacaagtcca aatgattcta 11580 gtttaactgc acttgaactg gaaatggaaa acaaaatggatagtgttatt actgaaagag 11640 ctgctaaaca cattgtcaat gaactttcta tttcactgcgtgatattgaa aacactgaag 11700 agtgtcatga agtgagtttc catgcacttt tatgtgcgcgtttttttaga aacaagaggt 11760 acaacctctc taatgcaggg agatacaaag tatctagaaagttacgttta acagaacgta 11820 tttatcaaaa aactctggca tgtgatttgt tcttaaaagatggcaagcta cttttaaaaa 11880 aaggtacttt acttttaaaa gaagagattg acaaaatcaaacaagctgct aagaacaatg 11940 aaattagttt tgttaataaa atgcaactta caactgatggtaaggctgtt gatttagcaa 12000 aagaatcact cttttatgaa acgatagatg tatatatcactaatgataat cttagtgttt 12060 cagtaccagt tatagggatc cataacgaaa atgatctgaacaaagcaatg actctcagtg 12120 atttcatcgc ttcaattagt tatgtgatta atttaccttatggaattggt aaatatgatg 12180 atattgatca ccttggtaat aagcgggtta agttaattaatgaattaatt actgctaaat 12240 tagaaagcgg cttcactaga atggagcgct ttttaaaagaaaagttaact attgctgatg 12300 gagttaaccg tggccagcaa attaatgaag agggtcaggttattgaacaa ggtgaaaaaa 12360 aggaattaac tattaaatct ttaatcaact caaaaccaattcaaattgtg attaaagact 12420 tcttcaatac ccaccaatta acccaatttt tagaccaccaaaacccttta tcagaattga 12480 gtaataaaag aaggatttca gcaatgggac ctgggggaatatcaagagag gaccctaatt 12540 tagatatccg tgatgtgcat tattctcagt acggtagaatttgccctatt gaaacacctg 12600 aagggatgaa catagggttg atcatgtctt tagctagctttgctaagatt gatgaaaacg 12660 gatttttaat ggcaccttat cgcaaaatca aagctggggtaattactgat gaggtggaat 12720 atttaactgc gcttagagaa gatgaacata ttattgctgagatctcttca cttgtcaata 12780 ttagtaacga taacaagatc ttagataagg aaattattggtaggtatcga tctatgcaag 12840 gactttatga tcctttaaag attgattaca ttgatgtagcaccacaccaa gttgtttcca 12900 ttggttcttc tttaatcccc tttttggaaa atgatgattcagctagagca ttaatgggaa 12960 ccaacatgca acgtcaggcc tatcctttaa taaagccatatgctcctgca gtaggtactg 13020 gtcaagaaca caaaattgct agtgattcag gtttaacaatgtcctctcct tgctcaggtg 13080 ttgttagtta tgttgataac agtaagatta ttattacaagtgatagttct aaaaaagaga 13140 cagttaacct agttaaattt gaacgttcca accaaaatacttgttataac cacaaaccaa 13200 ttgttgaaat aggccaaagg gttaataagg atgaaatcattgttgatggc cctgctgtta 13260 ataagagtga gttggcatta ggacagaatg ttttagttgcttttacaact tgaaatggtt 13320 ataactatga agatgcaatt gtcatttcag aacgattagttaaggaagat attctcactt 13380 cattaaccat taatgagtat gttgctcaat gtttgtctactaaaaatggt gatgaacaaa 13440 ttacccgtga tatccctaat gttagtgatg caaacaaacgctatcttgat gagaatggca 13500 tcattatggt gggtgctgaa gttaaagaag gggatgttttggttggtaaa gtttccccta 13560 aaggtcaagt cgaagtctct cctgaagaaa agctatttaaagccatcttc cctgaaagtg 13620 ttcaaaacgt gagagactct tcacttaaag tttcccatggtggggatggt attgtttcag 13680 ctgtaaaacg tttttcaatt gctaatggtg atgaacttaatgatggtgtg attgaaatga 13740 tcaaggttta tgtggttcaa aaacgtaaga ttcaaattggtgataaatta gctggtagac 13800 acggaaataa aggagttatt tctaaagtgg tgcctattgaagatatgccc catttagaag 13860 atggaacccc agttgatatt ctgctcaacc cccttggtgttcctagtcgg atgaacatag 13920 gacaaatttt tgaaacccac ttgggttatg cagcacacaagctagcagtt cgttctttaa 13980 ttagtagttg ttttgatcaa aataaagcta aggagtttgccattgaaatc aatcaacctc 14040 aagcaagggt tgaaagatta attaaaggtt taaaaaaccaaatcaatgat cgcaatatta 14100 aaagtgaaaa agaagcactt gaaaaactcg ataacagtgacattagttta gttttgaaag 14160 agatagggat gtcttttgat gatcttattt acaaaattgcaacccctatt ttccaaggag 14220 tgaacttctt agatctccaa gatgttatgc aagaagcaggattagatccc caaaaaaatc 14280 agggtaagtt taaactcatt gatggtagga gtggaatgccatttgaaaga cctatttcac 14340 ttggaattat gtacatgatg aagctgaatc acatggttgatgataagatc catgctcgtg 14400 ctgttggccc ttattctaag atcactcaac aaccattaggtggtaaatcg caaaatggtg 14460 gacagcggtt tggtgagatg gaagtgtgag cattagaagcttatggagct gcttataact 14520 tgcaagaact tttaaccatt aaatctgatg atgtacaaggaagaaatagg gcttatgctg 14580 ctattgttaa aggtgcagct ttcccagagc ctggtatccctgaatcattt aaattattga 14640 caaaagaatt acagggcttg gctttatctg tttcatttatctatgatgac aacacccaac 14700 aagactccaa taatgtttcc atcttgcaaa gtgatggggaacaagatgaa tttttcaatg 14760 attttgaatt tgacactgag ggttattaga aattaacaatgacaacaaca agacgtaata 14820 aaagaaataa caagctttat aaaaacatta aagcaattaaactttccatc gcttccaatg 14880 acaccatttt gaactgatct gaaggggaag ttacaaaagctgaaaccatt aactataaat 14940 cattaaaacc agaacctgga ggcttgtttg atgaagcaatctttggacct gttaaggact 15000 atgaatgtgc ttgtggcaag ttcaaaaaga ttaaataccgtggtgtgagg tgtgatcgct 15060 gtggggtgtg agttactgaa tctattgtac gtagagaaaggatgggacat attgcacttg 15120 tgagtcctgt agctcacatt tggatgtcaa aagaattaccatctccttcc aaaatatcat 15180 tagttttaaa catctcttac aaagaggttg aacaggttttgtactttgtt aactacatag 15240 tacttgatac aggtaagatc aaagatgata aaatcatgccttttaagttc aaagaagttt 15300 tggacttaac tggtaagggt tcactttcaa cacgacaaaaaatgcgtcgt gtgataggtt 15360 atatcttcag aaatctcatt aaaagtaaga gtagtgaagattaccgtaag ggaaaaatct 15420 tttatgaaag tttaaaaaac agctctctcc ccttttctctaaatgatgct tttaattaca 15480 ttaagaagta cactggtttt agggttggaa taggggctgaagcaattttg gaattgctta 15540 ataaaatcga tcttaacttg gaatttagca ggttaaatgatgctttaaga aaagccaaga 15600 aagatagtgt tgaagatgct aaagttaaga agatcttaagacaactggaa actattagtt 15660 ggtttagaaa ttctaagctt catcctaaaa acatgatcttacatactgtt ccagttatcc 15720 cccctgatat cagacctatt atccaacttg atggtgctaagtttaccacc agtgacatca 15780 acaattttta ccgcagggta atcattagaa atgaccgattaagaaggatt ttggaagatg 15840 gtactgtacc ttctattgtt gttaacaatg aaaaaagacttttacaagag tctgttgatg 15900 ctttatttga taactcttca cgtcataaac catcactttccaaagacaaa cggtcattga 15960 aatctttaac agatcgttta aaaggaaaac aaggtttatttagacacaac ttacttggta 16020 aaagagttga ttattcaggt agaagtgtaa ttgtggttggccctgaattg aagatgtatg 16080 aagttgggat cccagcacta atgatcttaa agctgtttaaaccctttatt atccatggat 16140 tgatcaataa gtttgatgaa aatggtaatg agattagaccaattgccgct tccatcagac 16200 aagctgaaga tatgattaaa aaccaggatg atcttatctggggaatagtt tatgatgtta 16260 tcaaagatcg tcccgtttta ctaaatcgtg ctccaaccctacataggtta gggatccaag 16320 catttgaacc aagaattgtt gatggtaaag caattagattacacccatta gtaactactg 16380 catttaatgc tgattttgat ggtgatcaga tggcagttcatgttccttta agtgagaatg 16440 cagttaatga agcaagagct gttctgcttg catcaaaacatatcttaggt ttgaaagatg 16500 gaagacctat tgtaactcct actcaggaca tggttttaggtaactattat ctaaccacag 16560 agagaaaagg acagttggga gaggggatta tcttcagcacagtttatgaa gcacgtgctg 16620 cttatgaaag tcaaaaggtt catttacatg ctattgtagggataagtact aaagcatttc 16680 ccaacaagaa gtttgcatgc caaggaactt taataacaacagttggtaag attatcttta 16740 atgatgtttt aggcaataat gttccttata ttaatgacggggaatttgat gaaaatgcat 16800 gtcccgaaaa gttcattgtg aaacagggag aagatgtaagacaatcaatt ttaaagcatc 16860 aaattatccc tgcattttcc aaaaaggtta tttccaagttaatcgatcta ctctatcttt 16920 tattggaatt taaagacctt cctaaaacac ttgataatatcaaagcactt ggctttaagt 16980 actctacttt ttcttcaact actgtttcag tatttgatatccctaagtac accaataaac 17040 aaaattactt tgatagtgct gatcaacagg tgctgaaatacaaacagttt tataacaagg 17100 gtttgttaac cgatgatgaa cgttataaac gcgttgtgaagttatgaaac aatgtgaaag 17160 aaaaagtatc tgatgagatc caaaacttaa ttaaacaagaacagtaccgt gataattcca 17220 ttgtggtaat ggctgattca ggtgctagag gtaacatttctaactttacc cagttatttg 17280 ggatgcgagg cttaatgtct aaaagcttta actatgaaagaaataaccaa tctaagatca 17340 ttaaagatac gatagaagtt cctattaaac actccttttttgaaggtttg accattaatg 17400 aatacttcaa ctcttcttat ggagcgagaa aagggatgacagatactgca atgaaaacag 17460 caaagtctgg ttatatgaca agaaagctag tagatgctactcatgaatta attattaacc 17520 atgatgattg tggaacaaga aaaggaattg ttgttgaagcaattgttgaa accaaaacca 17580 aatccttgat tgaatcatta tttgacagga ttgttaatcgctactcaatt actcctatag 17640 ttgatcctga aacacaaaaa actattgtag aagctaacagtcttattaca acgcaattag 17700 ctaaacagat ttgtgcaaca tctattaaag aagttttagttagatctgtt atctattgtg 17760 aaagggaaaa tggtatctgt caatactgct ttggcattgacttgtcaact ggtaagttgg 17820 tggaattggg aactgctgtt ggggtgattg ctgctcaatcaattggtgaa cctgggaccc 17880 aattgacaat gcgtactttc catactgggg gagtttcaactgaaaacaac ttagcacaag 17940 gctttgaacg tttaaaacag atctttgaag tagttactcctaaagatttt gaaaaagcag 18000 ttatctctga agtgaaagga acagttaaat caattactactgttcaaaac gctcaggaag 18060 tagtgattaa atcaaacgtt gatgagagga tttatactatccctttcagt gctcaaatac 18120 gtgttcatgt tggtgatcaa gtttcaccag gttctaagattacagaaggt tctgttgata 18180 ttaaacaact tttgcgaatt gcaggtatcc aaagggtaagacaatacatg attgtagaga 18240 tccaaaaagt gtataggatt caagggatag atattgctgataagtatgta gaaattatta 18300 tcagacaact aactaatttg ttgcaagtaa cagatgcaggtaacagcaat ttatttgttg 18360 gtcagttagt gcatagccat tatctcaatg aactaaataagagcttactt ttagctggaa 18420 agatgcctgt tattgcaatt aatcaggtgt ttggaattgatgaagcggca agtaaatcta 18480 actccttttt aagtgctgca tccttccaag ataccaaaaaaatcctaact gatgctgctg 18540 ttaagaacca agtagactat cttttaggtt taaaagagaatgttattatt ggtggaaaaa 18600 ttccagcagg aacaggattt ttaactgatg aagagttaactttcttaggt agcaaaacag 18660 ttgctgaaga gtattaaatc agagtaattt tattaatatttatctaactt acatctgatg 18720 tataaatcag taataaacat agttttattt tgtccagaaattcctaataa cactggcaac 18780 atcgtacgta gttgcactgc ttttaaagct aatctacacttaattaaacc ttatggcttt 18840 ttcttaaatg ataaaaggat ggttagagct ggtttaaattgttgagataa aattcaatta 18900 tttgaacaca aatcatgaga acatttctta caagcaaccactgaaaataa aactatttgg 18960 cttttaacta aaagtggtga taaaactcct gatcaaatttgcatgacaaa taaattacca 19020 aacgaacttt actttgtttt tggtcaggaa acaaagggattacctaaaac aatcatggat 19080 aactttaaac aaaaccaaat tagaattccc atttgaaatagtgttagaag tattaatctt 19140 gctaatgcag ttgtctgtat tttgtatgaa tattcaaagcaaaatcaata ctctaattta 19200 gataaacagt gcgcttaatc tgatcttatt aatgcaattaaaacttcttt gaataactat 19260 gaagaataaa gttttgaaac taaaaaataa taagatttttgataaaaaac tagcaacttt 19320 tttaaagaat ttagatattt ttcctaataa ttgagaattttttgaaaaag cttttattca 19380 cgcttcttac atcaatgaac atgaagatgt tagtgaaagttacgatcgct tagagttttt 19440 aggtgatgct ttaattgact ttgttgttgc taaaaaactatttgaacttt atcctaaata 19500 taacgaaggt cttttaacaa gaactaagat tgaaattgttaagggtgaaa atcttaatcg 19560 tattggtatg gagctaaaat taggtgattt tgttaagttaagcaatggtg ctgaactaac 19620 tgaaaacact gttggtgatg tacttgaagc tttggttggcgccatttatg aagatatggg 19680 gatgaaaaaa gcaactgaat ttgttgaaaa atatatttttgaaagaactt tttctgagat 19740 tttaaaatac gatttctttt cactttttca agagcaaaaattacctgaac caagagttag 19800 ggtaagctta acttcaaata atttggtact tagtataattgaacttgatg gtgatattat 19860 ttgatcacaa gctatcccaa ataacaaaaa ttacgatgataaaagtgttt tagagcacaa 19920 cgcaatggct tcttttacaa gttttttaaa aagtagtaaaggaagccatt tttttagtga 19980 tttaaaagag aagatagaaa atcaaaagat gtgtaagaaactagctatta aacctaaaaa 20040 aaattagaat ctatacatct aaacaaatta acaaagccatttaacttatg gactcaacct 20100 ttcatgagct tgggatctct caaactttaa ttgaaacgcttaatgcgctt catattaata 20160 agccaacaaa aattcaacaa atctctatcc ctcagtttttatcagaaaaa aacttaatag 20220 ttcactcgcc aacaggaact ggtaaaactg ctgcttttgcaattcccata attgagaagc 20280 tattaaaaga agatcaaaca gcaaaaccaa ctttagtaattgctccaaca agagaattag 20340 tagaacagat taaaaccaca ttttcaaata ttgctaaaaataaaaaacta agaattatta 20400 gtttaattgg tggtgtacct gcttgaaaac aaatcaaaaaaatcaaaaca aatccccaaa 20460 taatagttgg tactatgggt agaattatgg atcttttagagcgtaaagca attcatttta 20520 gcgatttaga acacctaatt attgatgaag ttgatttaatgttagaccgt ggttttaaaa 20580 aacaaatttt taatttacta gaacaaatca attcctttaaacaaattgct gtttattcag 20640 ctagttacaa ccaagaagct attaacattg ccaagcaaattactaataat gggatcttta 20700 ttggatcacc tgaatttaat aaagacgcaa ataccaataatgataaacta atcaaacaat 20760 ttgtttgtta tctattttca gatcaaaaaa agcaagctttatacagcctt ataaaaacag 20820 cacaagttaa gtcaatcatt gttttttgtg acactaaaaaactagttgat gatcttcatg 20880 tatttttaag aaaaaatgaa ttaagaactt ttgcacttcatggtgataaa aaacaattta 20940 ttagagagag aaatcttaaa atctttgcca atacaaaacaacccacgatt ctagtaacta 21000 ctgatcttat tggtcgtggt atccatgttg aagcaatcgatatggttatc aattattcag 21060 cttgtttaaa tctagaagct tatataaata gaatgggaaggactggcaga aacaatcata 21120 aagggacatg tgtaactttc tgcacctcac aagaaaagaaagtctttctg aaaatggttg 21180 agaaaatcac tgataatcga atagctgaat gtaaacaaatggaaataaag ttaattcctt 21240 taaaaaataa agctaaaact aaaaaaggtg gtatttcacttgattgtgtt cagaaaatat 21300 atgccaatgc aaaaccatat gaccgtaata aacgtgtccctttagcaagt gatcttttca 21360 aaagtcgtat gcgccagcct gaaaaagcta tgcaaaagcaaaaaattcat gacaatgact 21420 gacaaagtaa tatgtaacta attttttcca ttacaaatgttttggtaaag attaaagagt 21480 tgacaaggac tcaactcttg cgctctaatg ctagtctttaaattttgctt ttgaataatg 21540 ttaagtaaat aatcaactgc aaaaaaatgc tttaagttattaattaacat cttccttctt 21600 tgattgaaac attgctttaa aaacagacca aacttaaagtcataactaac cgatttattt 21660 ttttctaata atattaaggt tgaatccacc ttaggtttaggtttaaaagc atgcctatca 21720 attttaaaaa ctgttgtaat agtcaaatag tattgacaaaaagcaccaaa ggcactataa 21780 tcactagaat taacctttgc cagaagccga ttagcaaactctttttgtgt cattaaaaca 21840 aagcttcgaa gctttgattc taaaaactta ttgattattggagatgtaat gctatatggg 21900 atattaccac acaataatgg acttaaattt tcaaaaaaactattaaagtc ctttttgaga 21960 atatcgcctt taactagttg gtcttcagtt aatatcttttcaactagaag atattcaatt 22020 aagcgtttat caatttctat ccccttgtaa ggtattttgagttttaacaa ataatttgtt 22080 aacgctcctt taccaacacc tatttcaaca attgcttgtggatttaaatt tttaacaaaa 22140 gcaaaaattc ttttaatgac gcttaaatta accgtaaaattttgacctaa tttacgtgaa 22200 ggaaaaaaac tattcacgct ctaaaatcaa atctaatttggaataatttt gctttctcaa 22260 ggacgtaaag ttttaaggca aagacgtttt aaaaatcgtgctcaactcac ggtttccagt 22320 gagcgttaaa aagagtcaca gcttaagaga acgcaaggtttttacaacca ttcttcaaag 22380 taaaaccagg ttctttggta cctttattaa cgcttattttattaagaata atcattctac 22440 ttgaagggtt gcaatatcaa ttgcaaaaac taaatataagctagcagtac aacgtaacct 22500 aattaagcgt cagatccgta gtatctttca acaaattagtaataatttag aaccttgaga 22560 tattttagtt attgtcaaca aaggctttat tgaattaacatttaaagaaa aacaaaaact 22620 ttttttgcaa ctattaaagc ggataaaaga agtagatgcctatcaaacta gcgcaaacaa 22680 ataa 22684 3 38459 DNA M.geniitalium 3gtagtgttaa aaacattgat atttaatttg gttagtataa atgttggatc caaacaaatt 60acgcaataac tatgatttct ttaaaaagaa actgttagaa agaaatgtaa atgagcaatt 120attaaatcag tttattcaaa ctgataaact aatgcgcaaa aacttgcaac aacttgaact 180tgctaaccaa aaacaaagct tgttggcaaa acaagttgct aagcaaaaag ataataaaaa 240gctattagct gaatcaaaag aacttaagca gaagattgaa aacttaaata atgcttataa 300agattcacaa aacattagtc aagatttact tctaaatttt cctaatattg ctcatgaatc 360agttcctgtt ggtaaaaatg aatcagcaaa cttagaactt cttaaagaag ggagaaaacc 420agtttttgat ttcaaacctt taccacatcg agagttatgt gaaaagttaa atttagttgc 480ttttgataaa gctactaaga ttagtggaac taggtttgtt gcatatacag ataaagcagc 540taaactactt agagcgataa ctaatctaat gattgacctt aataaaagca agtatcaaga 600atgaaacctg ccagttgtta ttaatgaatt aagtttaaga tcaaccggac aactacctaa 660gtttaaagat gatgttttta aactagaaaa cacccgttat tatctttctc caactttaga 720ggtacaactt atcaatttac atgctaatga aatttttaat gaagaagatt tacctaaata 780ctacactgca acaggtatta actttcgtca agaagcgggt agtgctggta aacaaaccaa 840aggaactatt agattgcatc agtttcaaaa aactgagtta gttaagtttt gtaaacctga 900aaatgctatc aatgaattgg aagcaatggt tagagatgct gaacaaatct taaaggcact 960taagttacct tttagaaggt tattgttatg tactggtgat atgggcttta gtgctgaaaa 1020aacatatgat cttgaagttt gaatggcagc tagcaatgaa tatcgtgaag tttcttcttg 1080ttcatcttgt ggtgattttc aagcaagaag agctatgatt cgttacaaag atattaacaa 1140cggtaaaaac agttatgttg ctactttaaa tggaacagca ttatctattg atagaatttt 1200tgctgcaatt ctagaaaatt ttcaaacaaa agatggcaaa attcttatcc cacaagcatt 1260aaaaaaatac cttgattttg acacaatcaa gtaagcaaga attataatta acactctaag 1320gatgcaagtg ataaatgaag cgttgttata ttacaacccc tatctactac gcatcaggta 1380agccacacat aggtcatgct tttaccacta ttttggcgga tgtaattaag cgttttaaaa 1440tccaaaacgg atatgaggct tttttgcttg ttggcagtga tgaacatggc aataaaatag 1500aaagtaaagc taaaagttta aatttagatc ctaaaacatt tgttgatatt aacgctcaag 1560cttttaagtt aatgtgaaag acccttaata ttagttttga tcactttatt agaacaactg 1620atgaaatcca taaacaacaa gttcaaaaaa catttcaaga tttatatgac aaaaaactaa 1680tttatcaaag tgaatgaaaa ggggcatatt gtgttgagtg tgaacaaaat tactttactt 1740ttaataaaca aacaatgtta tgtgaaatag gtcataatct cagtcttgtc caagaacctt 1800gctgatttat ttctttttct tctactaaaa attgaattga aacaacgata ggaaaaaatc 1860aacttaacat tattcctaaa tcacgtgctt ctgaattaaa aaataacttt ataaacaatg 1920gtttaaacga tttagcatta acaagaaaaa atgttacttg aggaataaaa gttccttttg 1980atccaaatca aacaatctat gtttggtttg atgcattgtt ttcttatatc accaatttag 2040gatttagaaa tggtgatcct aattttataa agtgatgaaa taatgacaat aaagaaagag 2100aagttatcca tcttatatca cgtgaaatca ccagatttca ctgcatctat tgaccgattt 2160ttctacactt acttgatatt aagttaccaa cccaattttt atcacatggc tggatagttg 2220atggtgaagg gagaaagatg tcaaaatctt taaacaacgt tatctctcca gaacaattaa 2280ttgatcaatt tggtgttgat ggtacaagat attgtttatt aaaagagatg cgtttagata 2340aagataatcg ttgtagtgtt agcatcttaa aagagattta taatgctgat cttgccaata 2400gttttggaaa ccatgtttca cgtacttttg gcatgattaa aaagtatcta aacggcaaat 2460tagaatacca aattattact gataatgcac ttcaaaaaat aatgatttta atagatgaat 2520caatcgttca atttgatcat tactttaaca gttatgaatt ttatagagcg attaatctac 2580ttttaaaaat tgtttttgaa ttaagtaaat taattgatga tttcaaacca tgagaattgt 2640ttaaaaatca ggaattctca cttttaaaac aactactttt tacttgtgtt aggtgtgtgc 2700aggtatgcta tgtgttgtta acacctatct tagtaaatac tgcttcaaaa gtttttcatt 2760tatttaattt cgctgatgat gcctgtagaa aagatcaatt aagagatgca actttattaa 2820aaaaaattat tatctctaat tcaatggaag ttttatttaa aagagtagat taaatattta 2880cccatataat ttcgaaatta taattaatga cacatgaact tcttgcaaaa accaagggga 2940gttaaagatt ggtttggtga tgaattagtt tattttaatt ggattgttaa aaaaataaga 3000tctttagcat ttaattgggg ttttagtgaa gttaaaactc cgttgtttga aaatgcacaa 3060ctttttcaaa gatctaatgc taatgctgat attgttcaaa aagaactata ccagtttttt 3120gataaatctc aaagagaatt agctttaaga cctgaagcta ctacaccaat agtaagactt 3180gcttgtgaaa acaaattaat gcaagaagca aattttccct taaagttatt ttgcattggt 3240tcaatgtatc gttatgaacg tccacaaaac aataggtttc gtgaacattg gcaatttagt 3300tgcgaagtat ttggtttttc caacctgttt atctttttag atacactttt gtttgctaac 3360tctttgcttg aagcacttgg aattactgga tatgtgctta aaattaataa tcttgctaac 3420tttgaaacac ttagtaagtg aaataaagcc ctaaaagatt atttaactcc atataaatta 3480gaactaactg agctttctca aaaaagatta gaaaaaaatc ctttgagaat tttagatgac 3540aagatagatc aaaaaaaatc atttgttaaa aatgctccta aaattactga ttttttagat 3600gcaagtgcaa aacaagattc agaattgtta aaaacacaac taaaaaaaca caatattagt 3660tttgaatgaa cagacaatct agttagagga ttggattact atactggatt tgtgtttgaa 3720tatgtaaaaa atcaagacac aattttagca ggtggagttt atgataactt agttgaagaa 3780ttaagtagta atccaactcc cgcattaggt tttgcttgtg gaattgaacg gttaattaac 3840tgtttagaaa ttgataaaaa agcatttatt ttgaatacta aaccaaagca gatgttagta 3900atttgcttat ttgaagaagc gcttgaagaa ttggtttgac tagctaaatt atgaagggaa 3960tataaccaag taactattta tcctaaggtt attaaagttg ataatgggat tagattagca 4020aatcgcttgg gttatacttt cattggcatt gttggaaaaa ctgattttga caaaaaagct 4080attacaatca aaaacttagt atctaaacaa cagaccattt acacttgaaa tgaacttgga 4140gaacgaaatg tgttttaaat gtgttttaac caacgaattt taattggctc aatttcaact 4200gaacaactca ataaaacaat agttattatt gggtgaatta aacggattaa aaagttaggt 4260gaaattaact ttattatcgt tggtgataaa tcaggaacta tccaagtaac ttgcaaagat 4320aaagaacaga ttcaacaact tacaagagaa gacatagtta ttgttaaagc caaattacaa 4380cgcttagata gtgttagatt tgaactgata aatccaacta ttaaactttt ttcaaagtca 4440aaaactcctc ctttaattat tgaagatgaa actgatgctt tagaagaagt taggttaaaa 4500taccgttacc ttgatctgag aagacgtttg atgcaaaaac gattgttatt gcgtcatcaa 4560tttatattag caattcgtaa ctgatttaac cagcagggtt ttattgaaat agaaacacct 4620accttatcca aatcaactcc tgagggagca caagactttt tagttcctgc aagaattaga 4680aaagattgtt tttatgcttt agttcaaagt ccacaaatct ataagcagct cttaatgatt 4740gcaggagttg aaaaatattt tcaaattgca agggtctatc gtgatgaaga tagcagaaaa 4800gatcgtcaac cagaacacac acaaattgat ttcgagatct ctttttgtaa ccaaaaaatg 4860attatgaatc tagttgaaaa actctttttt agtgttttct tagatgtttt tcaaatcaaa 4920ataaaaaaga cttttcctgt ttttaaattt tcagaacttt ttgaaagatt tggtagcgat 4980aaaccagatt tacgttatgg ttttgaaata aaagatttca cctcgctttt tcaagatcat 5040cagaatcagt tcactaaatt aattgaagca aaaggcatta ttggtggtat tgaacttact 5100aatattgagt taagtacaga caaaattaaa gcattaagaa aaattgctaa ggaccatgat 5160gtgagtttag aagttcataa taaaaataat tcaacattaa aaacttcaat taaatgtgat 5220gaaaaaaaca ctcttctgtt agtagcaaat aaatctaaaa agaaggcatg aactgcttta 5280ggagcaatta gaaatgagtt gaaataccac ttggatattg tcaaacctaa ccaatacagc 5340ttttgttgag ttgttgattt ccctctctat gattttgatg agaaaacaaa tcagtgaata 5400tcaaatcaca acatcttttc aaaacctaaa caagaatgaa ttgataattt tgaatcaaat 5460aaaaacgaag cattaagcga acagtttgat cttgttttaa atggttttga aattggtagt 5520ggttcaataa gaattaatga tccaattgtt caaaaaagac taatgaattc tttgaacatt 5580gacccaaata agtttgcttt tcttctagaa gcttatcaat atggtgctcc tgttcatggt 5640ggaatgggac taggtattga tcgtttaatg atgattctta atcaaactga taacatcaga 5700gaagtaatcg cttttcctaa gaataatcat ggtattgaag tccatacaaa cgctcctgat 5760aaaattgaca aagaggaggt taaatgatgg ataaaagaac tagtgaaata gcctgaaaaa 5820aacaggttct ttttttattt ctatttagta aatgcccacc tataaactaa ttgttggttt 5880aggtaactta ggtaaaaagt atgagaaaac tcgccataat gctggtttta tggtgttaga 5940tagactagct agtttattcc acttaaactt tgataaaacc aacaagttag gtgattatct 6000ttttattaaa gaaaaagcag caatcttagc aaaacctgct acctttatga ataatagcgg 6060tctttttgtg aaatggttac aagatcactt tcaaattccg cttgcaaaca taatgatagt 6120ccatgatgaa atagcgtttg atttgggagt aattaggctt aaaatgcaag ggagtgctaa 6180caatcataat ggcataaaat cagtaattag acatttagat actgaacagt tcaatcgttt 6240acgctttggg attaaatcac aaaatacgag taacatattg catgaacagg taatgagtga 6300attccagaat agtgaactga ctaaactgga agttgcgatt acaaagtctg ttgaactgtt 6360gaagcgttat attgaaggag aagagttaca aaggttaatg gaatattatc atcatggcta 6420gatgaaatca gttacagtca agcagttact acaaacccca cgaaaattta ataacaagca 6480gattaaacta tcaggttggg ttaaaaataa acgtgctagt gctaacatca tctttctagc 6540aattagtgat ggctctagta ttaataccct acaagcagta gtaaaacaag aagataaccc 6600ccaggttttc tcactgttac aaactgttaa tttagcaagt gctgttatgg tttgagggga 6660aattatctta accccaaaag ctaaacaacc actggagttg aaattaaagc aggtgagttt 6720attagcacaa gcagagtctg attatccact gcaaaaaaaa gaacatagtc aagagttttt 6780tagaagtaat gcgcatctaa gagtaagagc aaaaacttac tttgcagtga tgaaaataag 6840gagtgttttg tcacacgcaa tctttgaata cttctttaaa aatgatttta tcttagtgca 6900aagccctatt ttaactagta atgattgtga gggagcgggg gaaacatttg taattaaaga 6960tagtgaaact ttttttaata aaacgacttt tttaacagta agtggccagt ttggagcaga 7020agcttttgcg caagcattta aaaaggtttt cacctttggt cctactttca gagctgaaaa 7080atcccatact aatcgtcatc ttagtgagtt ttggatgatc gaacctgaaa ttgcatttgc 7140taacttaaaa gatttaatgc agttaataca aaacctaatt aaattcttaa ttaaaaaagt 7200gatggaaaat gctagtgatg aactaaatgt tttagcaaag caatttagca atgacattat 7260tagcaactta aagacaatca ttagtactaa aaaatttcca atcattgaat acagcaaagc 7320attagcgatt ctaaaggaat ctagtgatac aaaaaaaact aattttgaac taaacgactt 7380tagttttggt attgacttaa aaacagaaca tgaacgcttt ttgtgcgaac aatattttca 7440aaatcaaccg ctttttgtta ttaactatcc aaaggagtta aaggcatttt acatgaaaac 7500aaatactgac aataaaactg ttgctgcagt tgatctttta ttaccaaaga ttggtgagat 7560ttgtggggga agtgaaaggg aaagtgattt aaaccaactt aagaataggt gtcaatcttt 7620aaacattgac acaaaaagtt tgaactgata tcttgatatg aggaaatggg gttattttgc 7680tagtgcaggt tttggtttgg gctttgatag attattagct tatatatgtg gattggaaaa 7740catcagagat gctattccct ttccccgtgt acatggcacc attaacttct aattcattaa 7800aataaccttt aattacccta tcaattctaa taatgataaa gcgcgcaatt acagggattc 7860aagcttctgg aagacaacac ctaggtaact ttcttggcgt aatgcaaggt ttaaaacaac 7920tccaaagtca ataccaactg tttttatttg ttgctgatct tcatgctatt actgttgatt 7980ttgaaccaac aatgctcaaa gataacaact tgcaacttgt taaaacttta ttagcactag 8040gacttgatta tggaaaagtg aacttatttt tacaaagtga tctgatggaa cataccatgt 8100taggttatct aatgctgaca caaagtaatc taggtgaatt acaaagaatg acccaattta 8160aaacaaagaa attagcgcaa aaaagaaata gtaataacac cattactatc ccaactggtt 8220tgttaactta cccagtgtta atggctgctg atatcttgct ttatcaacct gatattgttc 8280cagttggtaa tgatcagaag cagcacttgg aattaaccaa tgatttagct aaacgtgtag 8340caaaaaaatt taagttaaaa ctgaaattac ctgtatttat agaaaacaaa gataccaaca 8400ggatcatgga tctatcaaat cctttaaaaa agatgtccaa atcaaatcct gatcaaaatg 8460gtgttatcta tctggatgat agtaaagaaa caatcatcaa aaaagtgcgc aaagccacaa 8520ctgatagttt taataagatt cgttttgcta aaaaaaccca acctggtgtt actaatttac 8580ttgttatttt aactgcactt ttaaaagaag aagttaacca taatttaagt aaaaaaatcg 8640gctctgatct tgttaaatat tatcagaata aaagttattt agatttaaag aatgacctca 8700gtagtgctgt tattaatgtc atagaatcac ttaaatttaa aaaagcacaa attactgatg 8760aaatggtatt aaaagtccta aatgatggta aaaaccaagc taaaaaagtt gctgatgaaa 8820cattaaaaat gttttataaa gcatttggtt taacatctaa tcagcttttt gattaagctt 8880aaaattaaga taaataattt tccaattttg ttttcaatga gtgatcgttt aaatgatcaa 8940gcccaacatc gcttgcagaa acttttaagg ttaaaacaaa ctaataatga cccttattta 9000gtaacaaaaa ctagtctaac ccattcttca aaaagctttc aagttgaatt tgaaaaatgt 9060tcagaagaag agttgaagaa aaaagcaact gtctcactag ctggaaggat cattgctatt 9120agacaaacct ttttaattat tcaagatttt gatggtcaag tccaacttta catcaataaa 9180aaaatccatc ctaagttatt tgattacttt aatgaatttg ttgatattgg tgatcaaatt 9240gttgttagtg gtaagccaat gttaactaaa acaaaggtat taactttagc tgttgaagag 9300atgaaaatca ttgctaagtg tttattggtt ccacctgaaa agtgacatgg acttactgat 9360attgaaaccc gcgctcgcaa gcgctttctt gatcttacct ataacttagc aatgcgtgat 9420gtttttctga aacgcactaa gattattaaa tcaatccgta gctttcttga tcaaaatggt 9480tttattgaag ttgaaacccc cactttacaa gctgttttag gaggagctaa tgctaaaccc 9540tttaaaaccc attacaatgc tttaaaagcg gatttttatc tcagaattgc taatgaaata 9600gcattaaaaa aactcattat tggtggattt aacaaggttt atgaaatggg taaaatgttc 9660cgtaatgaag gggttgatac tacccacaat cctgagttta ccagtattga aatatatcaa 9720gcttatgcag attttgaagt catgcttgtg cttgttgaaa agctgattca atcactttgt 9780gaaagcttaa accaatttag ctttaactga aataacaaaa cgattaatct aaaaacacca 9840tttcataaga taacaatggt tgaacttatt aagaaagtta cagggatcga ttttaattca 9900gtaaaagatg atcaatctgc cattttatta gcagaaaaac atcatgttaa actagcaaaa 9960caccaacaaa ataagcaaca catcattaat ttgttttttg aacagttttg tgaacaaaca 10020ttaattgaac ctacctttgt aacccattat ccaaaagcag tttctccttt agcaaaacaa 10080gatccttcaa atcctgaatt cacccaacga tttgaacttt ttattaatgg taaagagatt 10140gctaatgctt acagtgagct aaacgatcct ttagaacaaa gaaaaaggtt tgaacaacaa 10200cttgaagaaa aacagcttgg taatgatgag acaagtgaac ttgatgaatc gtttttagaa 10260gcattaagtt ttgggatggt aaacactgct gggcttggga taggtattga tcgtttggta 10320atgttgttat gtgaatgtaa ttctatccgt gatgttgttt tcttccccca gttgcgtgaa 10380cataaataga gagttaggtt taaaattccg ttcttaataa aatagagctg tggctaggta 10440cttggggatt gttagttatg atggcagtta ctttaaaggg tgagcgattc aaccaaacct 10500agctactatc caaggtttat tggagcaaag tttttcatta atcattggca gaaagataaa 10560ggtaattggt tcaggtagaa ctgataaagg ggtacatgcc atcaaccaaa cctttcatgt 10620tgatattaat ggtgaaatta atctcaattt gttaattaga aaaattaacc agttgattaa 10680gccccactgt atagttaaaa ccttggtatt ggttaacgat agctttcatg cgcggtttca 10740agttaaaacc aaggtgtatg aatatctgat taactgtggg aatttaaatc cgttgcaatt 10800taactatgtt tggcagttaa accagcaatt ggatcttgaa aaactcaaag ctgatgccac 10860tttattttta ggtaagaaaa actttcttag cttcagtagt tcgattcaca ctgattcaat 10920tcgcacaatt agtaaaatta ccatacaaaa agaaactaac caactagtta gactaacttt 10980ttttggcagt ggttttctca ggagtcaagt gaggatgata gttgcttgtt tagtgaattt 11040aaacactaat aaaatggcac ttgaaacagt tgcaaaattg tttgaacacc ccaagaaagg 11100gagttgtgtt gttaaagccc ctagttgtgg tttgtatctg aaaacagtgg tatatgaaaa 11160atagaatgat tttttgatct atatagcaca attaatataa cttcatgatt gatcaaaaca 11220agttaattac taagtgaaaa aaagcatttg caaaagctaa gaatttaact actttagtta 11280atcttaagaa cactttacac aacagtgatt taaagccatt actccaaaag attaaaaccg 11340ctacaaaact aagtgaaaaa agtagtttag gtaagcttta tcaatcactt gatattcaac 11400taactgatct gttaactagt tacaaaaaaa cctttgaaat aaataaccaa gttagtcaaa 11460aaccttcact tgatgtgatg ctaccagcaa cagagtttac caatggttct aataacgcac 11520tatatcaggt tattgataat ttagttgaat actttaaaag ctttttattc acaattaatt 11580ttgatagtga actgaccagt attagtgact gttttgatct tttaaatatc cctaaagatc 11640attccagtag gaatgaatct gattcttttt atatcgataa aaccagttta ttgagaaccc 11700attgtactgc taccacgcta aaagcagtca gaacttctaa aaaaactaat aatcctgata 11760tcagggttgt ctctttagga gcggtttttc gtaatgatag tgatgatgcc acccactccc 11820atcagtttac ccaacttgat tttatgtgga ttaaaaaagg gctttcatta gctaatttaa 11880agtggtttat taacaatatg atcacccatt tctttgggga aaatactttt actaggttta 11940gactatccca cttcccattc actgaaccct cgtttgaaat tgacattagg tgttggttat 12000gtcaaaatgg ttgttctatt tgtaagcaaa ccaagtgaat tgagatctta ggggcgggga 12060tcatccatcc ccaggtgatg aataacatgg gaattgggga tactgaaaat attactggga 12120tagcagcagg aattgggatt gaacgcttag caatgttaaa gtatgggatt gatgatatcc 12180gtgattttta tgataacaac tttaagtttt taacccagtt tactgactaa taacaacttt 12240aagtttttaa cccagtttac tgactaaaat atgttgatat caaaaaaaac acttggcgtt 12300ttaatccctg acatctttag tttttctaat gatcaaattg cccaaaagtt agaacaaatg 12360gggattgaag tggaatcaat taagcagttt aacagccctg attacctcca acttgcaaag 12420gttgtatcaa tccaacccca tccccatgac aacaagcttt ttatctgtga attacaaatt 12480gataaaaaca agtttattaa tgttgtttcc aatgctaata acattaacaa tcctgataat 12540atcaacaagt ttgtcattgt tgcaaaaaaa ggaactgagt tactcaacgg gttaattgtt 12600aaaacccaaa atattaaagg gatcatttca gaagggattt tatgtagcta tattgacatt 12660aaccccttca gtagacagat cattgaaaaa acagaagttg ctgatgcgat tatcattgat 12720catgttagca atgatcatga ctgaaaccaa tacctctcgt ttttaagttt ggatgatgtg 12780atctttgatg ttaaaacccc aactaacaga gcagatcttc atagcttaat ctttttagca 12840aaagaacttg gggtactttt gaaaaccaaa acctttttaa aacaaaaaag tagtgttgtt 12900aaccatgact tttttaagtt tcccctaaat ttaaaaaaca agttaaaagc gaattatttt 12960ggcggtttgt tcttaagaca aattaaccaa catagttcac cttgaacagt taaaggactg 13020ttaattaacc aaatgatcaa accagttaac tattatgttg ataaagctaa cttagtaaca 13080gtgttcaccg ctcagccaat ccattgtcat gatgcagata gaattgttgg taacattgaa 13140cttaaacaag caacccataa tgaaactttt gttggacttg atgacaagca atatgagatt 13200gaaccagggg atattgttgt ttgtgatgag aagggcatta ttgcactggt agggatcatt 13260ggttcaaagc gcacaatggt ccaacctaca acaactaaca tcttttttga agttgttaac 13320tgtaacagtg aaaccattaa acaaactgcc aagcgctttt tgatcaataa ctttgccagt 13380aagtttatgg ttaaaccgat tagcttatta gctactgata actgtttaaa ctacttacaa 13440aacagtttac taaccactga taacattggc aaaattagcc acttttcaag ttcgcttaaa 13500gttgaaccat ttagtaaaaa gctcacagtg aatttccata agatacgcca actaattggc 13560attgaaaaaa aggaactaac tgatcaaacc attaaaaaaa gcctcagtca actagggttt 13620aaagttgaca accaacttct caaaatcccc agttacagac aagacattaa tacctgacaa 13680gacattagtg aagagattgt gaagttaatt gatatcaata agttaaaacc aattgggatc 13740actagtagtt ttaactttga aaagtccagt tactttaaca cttttaatgc tttaacaaaa 13800ctaagaaaaa agctacaaac acttggtttt cacaacgtta ttacctacca gttaactgat 13860caaaaaagtg caaaaacttt taatttgttt aacttagaaa atttcatcac cattaaaaac 13920ccagtgtccc aaaaccattc tgtaatgcgt gttagcttaa ttgattcact gttaaaagtg 13980ctaaaaacca ataacaacta taagaatgaa ctggtgaaca tctttgagtt ttcctttatt 14040aaaacccaaa acaatagtga actgcacctg gcagtattat gagttgaaaa actgtttact 14100tctagtttca atcctatgca agggataagc aatgatgttt ttactatgaa gggattagca 14160aaactcattg ttgctaactt agggtttagt tgtgactttg aaccacttga tgatagtgac 14220tattttgtta ataatcaaag tttaaaaata gtagttttta acgaacagat cggttttatt 14280gggctaatta aagaatcatt gttaaataac tatgatctga acaataaacc catttattgt 14340cttgaaatca acttagatag gatgctctct tctctaaaca ggattgaaaa aaactacctt 14400ggttacagta aactacaacc tgtttgcaag gatcttacct ttagttttac caaccctgct 14460agtcactttg atcagtttgc taacatgatc aaaaggataa ctggcattga aagttgaaag 14520ttaattagtg tctttgaaac tatgcaaaac aaccaactga tcactaagta caccgttcgt 14580tattttctga aaaatgatgc taacaaacca ctaactaacc aaacaattga acttatcact 14640aataacttaa aactccagtg tgaaaaacta aaaattaaat tagatattta gttgtttgct 14700tgaaaaaact aatttttaag attaattaac aatggctaaa gtttacaacc aagaagttta 14760tgttcagttt ctcaaacaac atggttttgt atttcagagt agtgaaattt acaacggttt 14820aaacaatagt tgggattttg gtccattagg tgcagtttta aaacaacaaa tcaaacaagc 14880tttatataac ttttttatta aaaataaagc tgatgttctt ttagttgaaa cccctattat 14940tctcagcgaa ttggtttgaa aagcatcagg acatttagct aactttgttg atactttagt 15000tgattgtaag agttgtaaat accgctttcg tgttgatcaa attaatgctg aaataaaagc 15060taaaaaggat tggaatagtt ttaaagttaa ctgtcctaat tgtcataacc aaaattgatc 15120agaagtgagg gattttaact tactttttca aactgaaatc ggggttgtaa acaacgataa 15180acgccttgtt tttctccgtc ctgagactgc tcaaggtagc tttattaact ttaaaaatat 15240cttgcaagct aagaagcgta atttaccttt tgctattgcc cagtttggta aaagctttcg 15300taatgaaatc accccaggta acttcttgtt tagaactaga gagtttgaac agtttgaaat 15360tgagtggttt tgtaaacctg atgatgcaaa ttcgctgttt gaaaaacaat taataatggt 15420agaacagttt ctacaaacag tgttaaaaat taacccagaa ttgttaaaaa aacatgaata 15480tgatcaatca gaattggctc attatgccaa aaaaactact gactttttgt ttaattttcc 15540ccacggatta aaggagttat gaggcttggc taacaggggt gattttgatc taaaacaaca 15600ccaagagttt tcaaaaaaga gcatgagttt ttttgatagc gaattaaacc aacatttctt 15660acctttcata atcgaacctg cggttggcat tgaacggtta ttttatgcac taattgtcag 15720tagttatagg agagaaatta ttaatgagga agaacgggaa gtattgagtt taccatttga 15780cttatgtcct gaacaaatta ttgttttacc acttgtaaat aaacttaaaa aagaagcatt 15840ttctgtattt gaaacgctag caaaaacaag gtgaagagtg tgctttgaga caactggtag 15900tattggtaaa aggtatcgaa aagcagatgc aattggaata aagtatgcag tcacttttga 15960ctttgaaagt ttagaagata atgcagttac catcagagat agagatactt tagttcaaca 16020gcgaattgct atcaaagaat taccacaatg attcatgaaa aatggtcaat aaaacattcc 16080tatcattaat gaagcaattt gaacataggt ttatgattgt tgacagtgtt agtcaaaaac 16140caacaacact agttcaaaaa accattaaca tttatctctg tggacccaca gtttataacg 16200atttgcactt aggcaacacc agaccattaa ttgtttttga tgttttaaat agagttttaa 16260aaaaggctaa atataccgtt aattttgttc aaaacatcac tgatattgac gataagatca 16320tcaagattgc tcaacaacaa gaagtaagcg aatcagttgt tacaaaacaa caaatcactg 16380cttacaaatc acttttaaaa aaactaaata ttctgcctat taaacatatt caaatcactg 16440aaaaaatcga taaaatccct gactatattg atcaattagt aaatcaaaac catgcttatg 16500tttcaactca aaacaacgtt tattttgcag ttaattcact aaagcaatat ggttatctag 16560ctaaccgaat ggtgcattta gaagaaactg atactgataa aaagaacaaa ttggattttg 16620tactttgaaa gattactact gcagggatta aatgaaatag taagtgggga cttggcagac 16680caggttgaca tgttgaatgt gccttcttaa ttgattattg tttcaaaaat gaactcacga 16740tccacggagg aggagttgat ttaaagttcc cccaccatga aaatgaaaat gccttacaca 16800tggctttata taaccagccc attaccaaac attggatgca tattggtcat ttgatgattg 16860aaaaccaaaa gatgtcaaag tcattgcaga acttcttgtt agcagttgat tttcttaact 16920ttcatgattt tcgtgttttg cgttggatct tttaccaaaa acactatttg catcctattg 16980atctaaacca atcattgatt gaaaaagcta ataatgatat tcaaaggatt gcaaaaacac 17040ttaatgttgc tagaacctga ttagtttatt cagaacaatc tgagttgatt agtcccaagc 17100aatatgatcc agttttttca gctttacttg ataatctcaa ctttgccaat gcagttgctg 17160ctatctgaaa actaataaaa aaaattaata caagtattaa aactaaggac tttagtgtgc 17220tgagagaaca acttagtttc ttggaatgat caattgattt attaggaatt agctttaaat 17280ctatccatac taaacttaat gtgcgtttaa ttaaagagtg atcaatatta cacaaacaaa 17340aagcaatgga taaagctgat caaattagaa aaaaactaat taaaaaaatg ttgctgtaaa 17400actaaatatg caatcaagcg ttcttatcaa agcaattaga tgtacaatca caatttaatt 17460gaagaaaagt ggttaaaaaa atgaaaaaac aaagatgtta accgctttga aagcgatagt 17520aacaaaaaga aatattatgt ccttgacatg ttcccttatc cctcagcagc aggattacat 17580ttaggacatg ttagagctta tactatcact gatgtaataa gtaggtatta caaagctaaa 17640ggatttaatg tgatccatcc gattggtttt gatgcttttg gtttacctgc tgaacagtat 17700gctattaact ctaatcaaaa ccctggcagt tgaacagatc aaaacattaa taactttatt 17760aatcaattaa ctagttttgg ttttgattat gactatcatt taagtctcaa aacaactgat 17820ccacgttatt acaaatacac acaatggatc ttcagtgagc tgtttaaagc aaacctagcg 17880gaattagttg atattgatgt taattggtgt gaacagctag gtactgtatt ggctaatgaa 17940gaagttttaa ttgatagtaa tggcaacgca gttagtgaaa ggggttcatt ttcagttgaa 18000aaacgcaaga tgaaacagtg agttttgaaa atcactactt ttgctgatgc acttcttgaa 18060ggcttagata cacttgattg acctgaacca attaaagaga tgcaacggaa ctgaattggt 18120aaaagtaaag gtgttactat taactttcaa ctaaaagatc ataaggaagc tattgcaatt 18180tttacaacta aaccacaaac aatttttggg gttagttttc ttgcagtttc aaccaaccat 18240tggttagcaa aaaagatagc agaaacaaat aaaaaagtag ctagtttttt aaaaaaacaa 18300ctccagaaaa ccacaacttt aaagcaaaaa gcaactttat atgatgggat agatttatta 18360acaaatgcta ttcaccctct tacaaatgaa ttgatccctg tctatgttgc taactatgta 18420attgaaggat atggaacaga tgctattatg ggtgttggag cacacaatga aaatgataac 18480ttcttcgcac gtaaacaaaa gttgaaaatt atcaacgtca ttgataaaaa agaacggctg 18540caaaattcat ttgcatataa cggattaaca actaaagaag cacaagtagc tattactaat 18600gagttaattt cacaaaataa agcgaaatta acaactgtat ataaactgcg tgattggatc 18660ttcagtagac agcgttattg gggcgaacct tttccaatta tttttgatga aaataacact 18720cctcatttgg tagaacaact ccctgttgaa ttacccttac ttgagaatta caaaccagat 18780ggaagtggta attctccact aatgagaaat caagcttggg taaacatagt caaagataac 18840atccattacc aaagggaaac taataccatg ccccaatgag ctggttcttg ttggtattat 18900ctgggttatt taatgttgat taaaaaccct aatttttgac caattgattc aaaagaagcg 18960aagaaattat ttgatcaata ccttccagtt gatctttatg ttgggggtgc ggaacatgca 19020gttttacacc ttttgtatgc ccgtttttga cacaaatttt tgtttgacaa gaagctagta 19080tcaacaaaag aaccatttca aaaattaatt aatcagggta tggtgttagg tcctgatggt 19140aaaaagatgt ccaaatccaa aggtaatacc attaacccca caccacttgt tgattcacat 19200ggagcagatg ctttaaggtt gtacttaatg tttatgggcc caattagtgc tagtttaact 19260tgaaatgatg aagggttaaa cgggatgaga aggtgattgg atcgagttta taacttcttt 19320tttaatcatg ctgttgttac tgatcaagtt agtcaagaga caatctttgc ttacaatttg 19380tttttaaaaa acagttattg tcatcttgac aaacatgaac taaatctggt gattagtgaa 19440atgatgatct ttttaaactt tctctataaa accaaaaaaa ttagcttaaa ttatgcaaag 19500ggatttttaa cagtactgtc gttttttgcg ccctttcttg ctgaagaatt gaatgaaaaa 19560tgtggacttg aaccatttgt tgttaaacaa gcgatttctt tagttgatta tcaacttttt 19620gagactgcta aaactaaggt tattctttca attaatggca aatttaaagc agctaaagaa 19680tttactaaag gtagtttaga gatagatgtt ttagaatcat ttaaacagga taaagagata 19740aatgacattc tcaaccaacc gattgagagg gtagtttatg ttcaggatcg aattattaat 19800gttcttttaa aaaaataggg agtaattagt cgcaaccgtt aagattactt tttgctagat 19860gacaaaaaaa acacaagatc tcactagttg gtatgaccaa ctgctagtta aagcaaagtt 19920aatttgtcat ggtgaagtta aaggtacagt ttgtttttta aataacagtt gaggcttatg 19980gatggaaatc caacagcttt acaatgatgc aattgcaaat aaaaatcaat tgtctgcaat 20040tgctctaact aaattccaac caactactag tttttgttat caagtattcc aagtacaact 20100ccctaccctt tctttttaca gtgaatatca aaaggaaaaa acccatatca aaggttttaa 20160tcctgagctt tttttaatta atcaagttgg tcaaaaacaa ctcaatgatc ctttggtttt 20220acgacctact agtgagattg ctttttgcaa cttatggaaa aaacaagagt tatcttacca 20280tgatctacct ttaatttata accagtgaac tcaggttttt cgtgcagaaa aaaacaccag 20340accttttttg agaaacagtg agttttactg acaagaaact catgggcttt ttgtggatca 20400gagccaatct gaacaagctg ctattagctt ttgaaattta tatcaggatt taattattaa 20460caaactttgt atccctgctt ttgttggttt gaaaagtgaa agtgaaaaat ttgcaggtgc 20520taaaaacaca tggacaatag aagcaattat gcctgatgga caaagtttac aatgtgccac 20580tagccatgat ttaggtgaca cttttacaaa gagttttact atcagctatc agagtaaaac 20640taaccaaaaa atgactccaa gtagttttag ttgtgggatg tcaactagga tcttaggagc 20700aattttttta acccacagcg atgattatgg tttggtttta ccttggtatc tagcaagtaa 20760acaagtcaag ttatacctgt ttgataaaaa caataaccct aaaacaagag ctttagcttt 20820tttagtgaag gattttttag aaaaactcaa aattcgcttt agttttatag aaattaacaa 20880tcaactaggt aaacaacttt taaaaggaga aatagaaggt attccattac agatgattgt 20940tgataatgaa aaaactatta acatcttcaa ccgcttaaca cgtttaaaaa ccagcttaac 21000atttgcaaat ctccaaactg aatttgttaa tttagttaac aactaccata cagagatgta 21060tagaaaagca aatgatttag ttgaacaaaa actagcaaga gtacaaactt taaaggaaat 21120tgaacaagca ttcaaaaata aaaaggctgt tttatgtacc gtgaagttaa ctggtgaact 21180tgaacaacac ttaaagacaa aataccaagt tagtgttagg tgtgttttta aaaagtcaga 21240tgtaacacaa aactgtcctt ttacaaatca accttgtttt gattcagttt taattgcacg 21300tgcttactaa aatcgtacta attgctttaa ttactatgct ttttatcact atgaattgaa 21360caactgataa agtaaggcaa acctgattag attattttgc aaagaaagac catctggttt 21420tagcttcaaa atcactaatt ccgatcaacg acccatcatt attatgaatc aattcaggag 21480ttgctacttt aaaagattat ttcagtgcta gaaaaacacc accatctaaa cgccttgtta 21540atgcacagat atgtttaagg gtaaatgata ttgaaaatgt gggttttact tcaagacatc 21600aaactttgtt tgagatgctt ggaaattttt caatcggtga ttattttaaa acagaagcaa 21660ttgattttgc ttttgatctt ttagttaatt attatcagct agatcctaag cgtttttata 21720tcactgttta tgaagatgat gaaactactt ataaaagatg aattaagcat aaaattgata 21780aaaatcacat tattaagtgt gacaaaagtc gtaacttttg agacttaggt ttaggacctt 21840gtggaccttg cactgaaatc tattatgatc gtggtgagaa atttgatcct aaaaaaattg 21900gtgaaaaact tttctttgag gacattgaaa atgatcgtta tgttgagata tgaaacattg 21960tttttagtca atttaataat gatggtaatg gcaactatac agaacttgct caaaaaaata 22020ttgatacagg tgctggaata gaaagacttg tttcagtatt acaaaatagt ccaaccaatt 22080ttgatactga catcttttta aagctaatca aaataattga agctttttgt ccatttaaat 22140atgatcccaa ctcttacttt acattcgatc ctcaaaaagt gaaagaacag agttattttc 22200ggattattgc tgatcacttt aaagcaatca cttttaccat ttcagaagga gttttacctg 22260gtcctaatga gagaaattat gtagtaagaa gacttttaag acgtgcttta atagcttgta 22320agaaattgca attaaactta gcatttattg aaaagataat agatgaaatc atcgcttcat 22380atgagaatta ttatcaacat ttaaaagcta aaaatgaaac tgttaaacag gtagttttaa 22440aagagattaa tgcatttaat aaaacgattg atttaggttt agtgctgttt gaaaaaagtg 22500ttaaaaacaa tactctaact ccccaattaa catttcaatt gaacgaaaca tacggttttc 22560ctgttgaaat aataagagaa ctagttaatc aaaaaggttt aactattgat tgaacagtat 22620ttgatcagtt aatggccaaa catcgttcta tctctaagca aaataaccaa actataaatt 22680ttgaaaaaca aaatattaat ttagttaatt tcaaaactaa aagtactttt ttttatcaca 22740aaaataaaat taatgctaag gtaattggtc tttttgatga aaattattta ccagttaaag 22800aacttaataa tcaaagtggt tatgtagttt ttgaccaaac agttttatat gctacttctg 22860gaggacagag atatgatgaa ggaagttgca ttaatcattc taataataat gatcaaaaaa 22920tcagttttca aggtgtattt aaaggaccta ataaacaaca cttccactac tttttagtag 22980gtagttttaa actcaatgat caagtaactt tatcacatga tgaaacttga agaaaacttg 23040ctgctaacaa ccatagttta gaacaccttt tacatgcagc tttacaaaaa gaaattgatc 23100cacttattaa acaaagtggt gcttttaaat ctgcgcaaaa agcaactatt gactttaatt 23160tgaatcgtca tttaacaaga aatgaacttg agaaagtaga aaataaaatt cgctctttga 23220ttaaacaaaa aataagctca aaagagattt ttactgattt tgaagggagt caaaaactaa 23280atgcaattgc ttattttgaa gaggaatatt ctcaacatga aatattaaga gtgatccgct 23340ttggtgatta tagtgttgag ttgtgtggtg gcactcatgt agctaacact gcttcaattg 23400aagattgttt tattactgat ttctattctt taggagctgg aagatgaagg attgaaatca 23460ttagcagtaa tgaaactatt aacaactatt taaaagcaga aaatcaaaaa ttaatccaat 23520taaaatcaga acttgaaaaa gttctatctt tgattgatag ttcaattttt aaagttgagt 23580taaaagaatt gcaacaaagg ctagataaat ttatcttacc tgaaaaaatt acccaattaa 23640gagatgcatc tgatacttta ttagctttaa aaaatgatat taaccagtta aaaacaaaaa 23700actataaagt atcacagcaa gctttagctt tatcaattaa aaagcaatta ttatccttag 23760tagatgaaaa taaaagttat gtaattgcca cttttaatga cgtagaacct aaactattgc 23820tacaaacact acatgatgtt ttcaatcaaa atcaaactaa aaatttcttg ataattaatc 23880aattcaatga aagtaattca tttattgtta taggaaataa aactaccacc attattgaaa 23940aattaagaaa tagttttaat ttaaagggcg gaggcaatga taagttattt agaggttctt 24000ttcaggataa tgttacccct caaaagctta atgaattgtt tcaaaataaa gctttagttc 24060acaaaaaaat tttcgaatta ttcgttgaag atgaaagata aatttagttt tcaaaaaaac 24120tatgatttca acttagttag tgatgggctt tatgaaattt gaaataatgc tggttttttt 24180aaacctaaag ataaaaacaa ttcttttaca gcaattcttc cccctccaaa tctaacaggt 24240actcttcata ttggtcatgc ttttgaggtt agtattactg atcaaatcat gcgttttaaa 24300aagatgcagg gatttagtat taactgaatt cctggctttg atcatgctgg cattgctact 24360caaacgaaat atgaaaaaat agcattaaaa gaaaatcaaa aatattttga tgcagatgat 24420gataaaaaat ctgaaatgat catgaattgg gcattaaatc aaagcgaaat aattaaaaat 24480caactaaaga gtttaggagt ttgcttaaat tgatctgaaa ctaaattcac gctttcagaa 24540caagctaata aaattgttaa caattgtttt aaaaaccttt atgaaaacgg ttttatttat 24600caagcataca cgcttgttaa ttgagataca aaattgaata ctgctatatc aaatattgaa 24660gttatcaata aacctgttaa tcaacatctt cattatgttg tttataaact agcgaatgat 24720agtaaacaag aactaatagt tgcaacaaca agaccagaaa ctatctttgc tgatgtttgt 24780ctattggtaa acccaaaaga taagcgctat actaatttct gaaataaatt agtagttaac 24840cctttaacag gaaaacaaat tcctgttgta acagatagct atgttgacat taaatttggt 24900acaggaatat tgaaatgtac tcctgcacac gactttaatg actatgaaat caacactaaa 24960tataaatttg attttctaag ctgcattgac agtaacggta ttctcaatca aaatgcaagt 25020aaatttcaag gccttagtgt tttacaagca agaaataaaa ttgttaaatg attagaaaaa 25080aataaattac ttgttaaatc aataccatta actagtaatg ttggtttttc tgaacgcagt 25140ggcactgttg tagaacccat gctttcaaaa cagtgatttg ttgatttacc aaagttaaaa 25200gatcacttat atttaaaaaa atatcctgat tttattccca aacgctttaa taagcaagtg 25260tcaaattggt tgaataaact caaaccatgg tgtatttcaa gacagttaat ttggggtcat 25320aaaattcctg tttgatttga aaacaataca ggtgaaatag ttgttggtga aaaaccttca 25380aaaaatttac aaaactacac tagatcaaaa gatgtacttg atacttgatt ttcttcttcg 25440ctttgacctt taatttgttt gaattgagaa caggatgact cttttcatga aactgagctt 25500ttagttacag gttatgatat tctatttttc tgagttttaa gaatgttatt taactccttt 25560tttgaaacta aaaaactgcc atttaaaact gttttaatcc acggtttagt acgcgatgaa 25620caaaatcgta agatgtcaaa atcactgaat aatggcattg atcctgttga tcttattaga 25680aattatggag cggatgcagt gcgcttattt ttgtgttcaa atcacactcc aggagatgat 25740ctaattttca gcgaacaaaa aataaaaagt gcatgaaatt ttttaaataa attgtggaat 25800gttactaagt ttgttatcca actagaaaat gatcaagaaa ttagttatga cttggacaaa 25860ctttcattaa gtgaaacttg aatcttagct aaattagata aagtaattca aaaaataact 25920aagctactag ataaattcca gttagcatta gcaaaccaaa ttcttgttaa atttgtttgg 25980gatgattttt gcaatacttt cattgaagca attaaaaaag aaccaaatca actaaaacca 26040cagctttttt atactgctaa atcagtttta tctaatattg ctattttgct tagtatcact 26100gttccttttt tatctgagcg tatttatcag caatttaaca ataaaagtgt tatgcaagca 26160acatgacctc ttgcaactaa aattaaaatt cccaaacttt ttgatcttgt tttagctgct 26220attaatgact tacgcaatta cagaaaacag tacatgctta attcacaaca aaaactagtt 26280gttatcttat ctggtaaaaa tgctgttgat gttaaacaat actttaactt tagttgaatt 26340gaactgaaaa ttgaaactaa taaaaaagtt agttttaaat accaaattgt tgatgataca 26400acccaaagac ttaaatctct acagaagcaa caagcttttt ttgaaagtga agtaaaacgt 26460agccaagcta ttgttaaaaa taaaagcttt ctagaaaaag cacccaaaga aaaggtaaaa 26520agtgaatttt taaaattgga agaatatcaa aaaaaactta ctgaaaccaa ccaattaatt 26580gctaaattaa ctaaagctca ttagaagaat ctttatcttg ttaaattaat acttaactgg 26640tttaatgtct gcaattaaat ttaatcctag ttcattcaga aaaaacttta aatggtttga 26700aaataacaaa aattggatta attttgataa tgctgctact tccattgcac ttgatgttgt 26760ggctgaagca agcaaagaat attaccagta tttttgtgtc aatcctcata acaaaaatcc 26820tgaaattaac caaaaactta ttgctattat tgaagaaaca agagatttat tagcaaaatt 26880tttcaatgct aaaaaaaatg aaataatttt tacaagttct gcaactgaat cgcttaactt 26940attcgccttt ggattaagct ctttagtaaa aagtaatgat gaaatcattc tcaaagaaga 27000tgaacatgct gctaatgttt ttccctgagt aaatctagca aaagaaaata aagccaaact 27060aaaaataatt aaaaaaacac caaataaatc ttgaactgat gcttttttaa aagcttgtac 27120accatcaaca aaactattag ttataactgc aacatctaat ctttttggaa atagtattga 27180ctatgaaaaa atttctaaac acttaaaaaa aatatcacca aatagcttta ttgttgtaga 27240tgcagtacaa gctgtaccac accataaaat cgatattaca agtgctaata ttgatttttt 27300aactttttct acacataaat tttatggacc tactggtctt ggcattgcct ttatcaaaag 27360cgaattacaa tcacgactaa aaccctttaa attaggtggt gatattttta aatcattgga 27420taataacttt aagataattt ttaaagaagg tccttccaaa tttgaagctg gaacgctaaa 27480tattatggct atttatgctt tgaataaaca gttaaaattc atgcaaaaag aatttaattt 27540cagtgaaatg gtgttttaca gcaaacaatt aaaaaattta gcttatcaac tgctaagtca 27600aaatcctaat atcgttttag ctaatcatga tcaagatgtt cctatctttg cttttaagca 27660taaatatatt aattctgcag atctagcaac ttttttaaac attaaaaaaa taattgttag 27720acaaggatcc atctgtgttg gtaaatttaa aaataaagag agttttttac gtgtttctct 27780actccattac aacacaaaag aggaattact ttatttagaa aaattattaa aaactagtaa 27840gaattccatt attaatgaac taatatatta gatgtaagtt agataaatat taataaaatt 27900actctgattt aatggactta aaaaagacat tgttaatgcc taaaacatcc tttgcgatgc 27960aggcaaattt atctactagt gaaaagaatt ttcatgattt ttgaaaagat aaaaaagtct 28020ttcaaaaatt aaaaaaacag aataaaggaa aacagataaa aatactgcat gatggaccac 28080cttatgcaaa tggtagtatt catgtgggac atgctcttaa caagatttta aaagacttca 28140ttttacgtag ttggttatat gaaggatatg atgttgtttt tattcctggt tgggattgtc 28200atggactacc aatagaacat gcagttagta agaaaaaccc tagtagttat agcaatcttt 28260caactgttga aaaaagaaaa ttatgtcatc agtttgcact ttcacaaatt gcagttcaaa 28320aagaacaatt tcaaagactg ggacttttaa atgattttca aaactgttat tacacaatag 28380atgagagttt tcaatttaag gaacttgaac tatttttaca agcaattaaa aaagggctca 28440tttttcaaga tttaaaacca acttattgat caccaatttc aagaacttca cttgctgaag 28500cggaaattga atataaagaa gttaattcaa ttgcacttta tttaactttt aaagtttcta 28560aaagtgattt tttagatgaa aatgctaatt tattagtttg aacaacaact ccttgaacac 28620taccaactaa tcaagcaatt gccattcatc ctgattttga ttatcttctt tttgaatata 28680accaacaaaa atttgttatc ttggaaaaat tatttgaagt ttttacaaat aagttaaatt 28740gaacaaatgc aattaaacta aaaaaattca agggttcaaa tttaaaaaat tcaagctatt 28800ctcattgttt ttataacaag gttttaccag ttctaatggg aatacatgtt gttgataatg 28860agggaacagg tattgttcac agctcccctg catttggaat tgatgatttt tatctttgtc 28920aaaaaaacaa gattaaagaa gttttgattt ctattgatga gaaaggtgta tttaataact 28980tacttaatga taaagaactt gagaattgtt tttatcttaa agcaaatgat ctaattatta 29040atcgtttaaa acaaaacaat agctttattt tttctgaagt tatttcccac cgcgaaccac 29100atgattgacg ctcaaaaact ccagttatat accgtgcttc caaacaatta ttcattaaaa 29160ctaaatcaat aaaaaagcag ttaaaaaaac aaattaatca agttaatttt ttaaattcaa 29220aaaatcaatt gagattaaaa gagatgcttt tacaacgtga tgaatgatgt atctcacgtc 29280aaagagtatg gggcttgcct ataccaattg tttatgcaaa taacaaacca ttgttagatt 29340tttcaacaat tcaatacaca attaaacaat tgaaaaagca tggtattgat agttgatttg 29400aaaaagatgt aacttgtttt ttaaaacctg ataaaaccaa aaaatgagtt aagtatcaca 29460aggagattga tacattagat gtttgatttg actcaggttc ttcctataat gttttggaaa 29520taaataaata tggttcaata gctgatcttt atattgaagg ttctgatcaa tatcggggtt 29580ggttcaactc ttcttcaaat tgcggaatta ttcaaaatga tttaatccct tttaaatcac 29640ttgtttcaca tggttttaca cttgatgaaa atggcaataa aatgtcaaag tcattaggaa 29700acatagttga tcctttaaaa atttgtgatc aatatggagc ggatatatta aggttgtgag 29760ttgctaatac tgattgacaa attgataaca aaataggtgt taatattctt aaacaagttg 29820ctgaacaata ccgcagaatt agaaatagtt tactacgttt tattttgggt aatattaatg 29880gatttaactt tacatcaatg gatgattata agttttcact agaagacaaa atagttatcc 29940ataaaactaa ttcactagta gaacaaattg agaaattttt agagaaatat aattttttag 30000gttgcctaaa agtgattaat aagtttgttt tatgactatc aagctgatac tttgaaataa 30060ttaaagacac cttatattgt gatgctaaaa ataatcctaa tcgtttagct aaacaagctg 30120ttttaaacta tatttttaca caactaatca gttttttaaa tatctttatt ccccacactg 30180cagaagatgc ttgaaaaaac tattcattca ataaaaaacc aataagtgtg aacctcttta 30240caaaaccgac tgtttttaaa gttgctaact ctaagaattt aggaaatatc tataaaactt 30300ttactagtat taaaaatgct gctttcaaag aaattgaaaa gctaagaaaa gaagggttga 30360tttctaaaaa taatcaaatt gaattaaccg ttggaattaa taaaaaaata cccaaaaaat 30420taaaggataa tctcgcactt tgacttaatg taaacagtgt taatttaaca aataatgaaa 30480atgaaattaa agttaaaaaa actaaaaaaa caatgtgtga aagatgctga aattttcaaa 30540caatcattaa gcaaaaatta gatcataatt tgtgctcacg ttgttttaaa gtgtgttaag 30600tatattatta tcttgattat attgtaacta gaaccatata tgtttaaaat tgttttcttt 30660ggtacttcaa cgctttcaaa aaaatgttta gaacaacttt tttacgataa tgattttgaa 30720atttgtgctg ttgtaactca gccagacaaa attaatcatc gtaacaataa aatagtacct 30780tctgatgtta agtctttttg tttggaaaaa aacataactt tttttcaacc aaaacaaagc 30840ataagcataa aagctgatct agaaaaatta aaagctgata ttggtatttg cgtttcattt 30900ggtcagtatc ttcatcaaga tattattgat ctttttccaa ataaagtaat taacttacat 30960ccttctaagt taccactact tcgtggtggt gcaccattac attgaaccat tattaatggt 31020tttaaaaaat ctgcattgag tgtaattcaa ttggttaaaa aaatggatgc aggtccgatt 31080tgaaaacaac aagatttttt agttaataat gactgaaata ctggtgattt atccatatat 31140gtagaagaac attcaccctc ttttttaatt gaatgtacta aagaaattct caataaaaaa 31200gggaaatgat ttgaacaaat aggtgaacct acttttggat taaacataag aaaagaacaa 31260gaacatcttg atcttaatca gatttacaag agttttttaa actgagtaaa aggtttagct 31320cccaaacctg gtggttggtt aagctttgaa ggaaaaaaca tcaaaatttt caaagctaaa 31380tatgttagta aaagtaatta caaacatcaa ttaggagaga tagttaatat atctcgaaaa 31440ggaattaata ttgctttaaa aagcaatgaa attatttcaa ttgaaaaaat tcaaatacct 31500ggaaaaaggg tgatggaagt aagtgaaata ataaacggaa aacatccttt tgttgttggt 31560aaatgtttca aatagagaat tagctttaat aattttgtta aaagagttag aagagatgct 31620tgcaggagtt cttttattac aaatatggtt aaaatgcaaa tatgctaatg ttcagtttgg 31680tgaacatggt tttaatggag atgaatttta tttagatttt tatataaatg agaatttttc 31740tacaaaacag tttgcaaaaa tagaatctga tttaaactct ctttctagta aactagaagg 31800gatttctcaa aaatttgttt ctttagatga agcattaagt ttttttgaaa atgatcagtt 31860tacaaaaaac ttattaaaaa aaagcaactt aaacaaattt aaaatcacct tttttgaaaa 31920taaacatttt tgaatagaag atttaacttt aacttttatt aaaaaaagtt ttattaagct 31980attaaatgta agcgtaaatt attttttggg agatccttca caattacaac ttcagaggat 32040taatggcatt tttgctcaat caaaaaaaga attagaacaa ttaataaaag aaaatgaaga 32100acgcttgaag aaggatcaca gatctttagg taaacaatta gagttattta gctttgaccc 32160actgatcggt gcaggtcttc ctatttgatt agcaaagggt acaacactaa ggaatataat 32220cggtaatttt gtgcatcacc agcaactatt gtttggtttt aatactgttt gttctcctgt 32280attagctaac atagagcttt ttaaaattag cggccactat cagcactata aggaagatat 32340gtttcctgct attaaacttg atagtcaagc aatgatgctt cgtcctatga catgtcctca 32400tcactgtctg attttcaaac aaaaacgata ttcatataaa aaaatgccac agcgcttttc 32460agaagattct attttgcatc gttttgaagc ctctggagga ttaataggat tagaaagagt 32520gaggtgcatg actttacttg ataatcacat tttttgtcgt gcagatcaaa ttaaaagtga 32580gattaaaaac gcatttaatt taattcaaaa agttaataaa aaatttggat ttatatttga 32640taggatagat ctttctctac atgatcctaa aaatcaatca aaatttattg ataatcctgg 32700tttatgaaga gaatctgaaa gccaaatgga gaatgtttta aaagatttaa atatccaata 32760tcaaaaagag ataggagctg ctgcttttta tggaccaaaa attgattttc agttcaaaac 32820aatctttaaa aaaatgatta ctattgccac cattcaacta gattttttac taccagaaaa 32880atttgatcta acttatatag ataaaaaaaa tacactaaaa aaaccagtta ttatccatgt 32940tggaattatt ggaacttatg aaaggtttat tgctgcttta cttgaaaaaa caagtggtaa 33000ttttccttta tggttagcac ctgttcaagc cgtaattatt cctgttaata tccaaaagca 33060tttaaaggca gcaaaaaaac tttataacaa attgctaaaa gaaaacatcc gtgtaaattt 33120agatgataat caagatcgct tagctaaaaa agttagacaa gcaatcattg aaaaaattcc 33180tttacaactt attgttggag ataaagaaat agagaattta gagaagttga catgccgtgg 33240ttttaaaggt gaaaaaatca ccagaattag ctttaataat tttgttaaaa gagttagaag 33300agatggatag gatttaatat tagccattta ggttattaat tagttttaga atgtttttta 33360tcatcaatga tttaaaagaa tgcattagcg ctttaaagct taaatttgat gaccaaaagg 33420aacttgttaa actagttaaa aataatagtt ttaatggttt ttcttcaact attattttcc 33480aactaaaaag tgaaaatcat aaaaaaattg cagatagtat tgttgagtga tttttaaaaa 33540ataaaaagga taactaccaa aatgttttta ttgctaacaa taattttata aactttcaaa 33600ttagctatca aaagtactta gaatacttga taaaaacacc ttgctttact aagaaaaata 33660taaagatttt aattgaatct gtatcagcaa atcctaccgg aaggatccat ttaggtcatg 33720tgagaatagc tttttttggt gatgttttaa acaatttagc caagctgttg ggttatacaa 33780cagtctgtga atattgggta aatgattatg gacaacaagc acgagttttt agctttagtg 33840tttatcaaag tttgcagtta aaaaaaaata ttgctatcca gcaacatcct gatggatata 33900gtggaatagt aatagataaa attgctagtg aaattgaaaa ttttccagtt gataatttaa 33960attttgaaga gttttgtaaa acatcattct tagatcattt tttagttaat tgcacccaaa 34020aagttttgtc tttaattaaa agtgatttga ataaaatcca tgtttttatt gatagttgaa 34080aatttgaaag cgaaattgtt aaaaaaacaa attttaatga tcttttagaa caacttaaac 34140caaatagtta tttttatcaa gataatgcac tctgactaaa aactacgctt tatggagatg 34200ataaggatag agttttaatt agaagtgata aaagagcttc ttattttgga actgatgttg 34260cttatcactt agaaaaatta caacgtggct ttgacattct atttaatgtt tgaggcactg 34320atcatgaagg acatattaaa aggatgtatt gtgcatttga tgctttaaaa aataccacta 34380aaacttcttt aaaaattttt gcattacaac tggttactct ctataaaaat aaagagctag 34440tacgtttgtc aaaacgtgct ggaaatgtaa tcacaattga aacaatgctt tcaatgatta 34500gtgaagatgc tgctagatga tttatgttat ctcaaaataa tggcacaatt atcaaaattg 34560atttagatat agctaatttg caaaactctg ctaatccagt ttattatgtt caatatgcgt 34620ttgcaagaat gaatagtatt cttagaattg caaattctga tcaattaaaa gaaattactg 34680attgcagtct tttgattaat gaaaaagaga tatcactttt aaatcaactt gtctattatc 34740cttttatgtt gcaaaaagct atggaaacag gcgaattgca cttattaact aactttttat 34800atgaaactgc tagtttattt cattcctggt ataaagtttg caaaattaat gatgataaaa 34860attcactttt atcagcacaa agacttgctt tattgagatc attacaattt atagttaaac 34920aaatccttga tgttttgaag atttcaacac cacaacaaat gtaatacaga cctgatttat 34980acaaaaaata cttagaaaat aaaagtgaaa atcactgttt taacactttt tgaaaacact 35040atttggcctt acttaaatag ttctattatg ttacaagctc aaaaagcaaa tttagttcaa 35100tttgaagtag taaattgaag aaatttttgc aatgataaac ataaaactgt ggatgatatg 35160gcttatggtg gaggaagtgg catggtttta aaagctgaac ctattattaa ttgtttaaat 35220ttttataaag ccccaaattc tcatgtagtt ttactctccc cagaaggtga acaattttct 35280cagaattgtg ctaaaaaact tacaaaatac gaacacttaa ttttgttatc tggtcactat 35340gaaggttttg atcaaagaat ttataaatat attgatcaaa ttgtttcttt aggtgatttt 35400gttttaagtg gtggggaact tgtagcacta agtgttattg atgctactgt tagattaatt 35460aaaggagtta ttaatgatca gagtcttatt tgtgaatcat tcaatgataa tctattagat 35520tttcctgttt atacaaggcc atacgattta aaaggcgata aagttcctga agttttactt 35580tcaggagatc accaaaagat tgaatcattt cgtaaagaac agcaaatctt aaaaactgca 35640aaatacagac ctgatttata caaaaaatac ttagaaaata aaaatgaaaa aaataaataa 35700gccagtttca gtttgtgcaa cagttttata aatcaatgcc atgttaatta atatagataa 35760tattttagta aaaatgttaa ataacatatt gcaatttctc aaagaaagag aactttattc 35820acaagctaat tttgaaacag aactagataa ccatttaaaa gagaaaaaaa ataactttta 35880tgttggtttt gatccaactg ctaattcttt acatattggc aattatgttt taattcacat 35940tgcaaaatta ttaaaagaca tggggcatac tccgcacata gttctaggga gtgcaactgc 36000tttaattggt gatcctactg gcagaattga attaaggaaa attttagaag aaaaagaaat 36060tgtaaaaaac accaaaacaa ttaaaaaaca aatcaaacag tttttaggtg atgtaattat 36120tcatgaaaac aaagtttgat tagaaaaact taattacatt gaagttatcc gtgaattagg 36180tgcttttttt tcagttaaca agatgttaag cacagacgca tttagtgcta ggtgagaaaa 36240aggactaact ctaatggaat taaactatat gatcttacaa gcatatgact tttattatct 36300acataaaaac cataatgtca ctttacaaat aggtggaagt gatcagtggg ctaatatttt 36360ggctggtgct aacttaatta aaagaaaaaa taatgctagt gtttttggat taactgctaa 36420tttattagtt aaagctaacg gagaaaaaat gggtaaaact agtagcggag cattatgact 36480tgatgaaaat aaaactagtg tttttgattt ttatcaatac tggattaacc ttgatgatca 36540aagcttaaaa aagacttttt taatgctaac aatgcttgat aaaaaagtaa tagatgaatt 36600gtgtaattta aaaggcccaa aaattaaaca aaccaagcaa atgctagcct ttttaattac 36660tgaattaatc catggcacta aaaaagcaaa agaagcacaa caacgatctg aactaatatt 36720tagtaatcaa ccagatcttg atattaagtt agtaaaaaca agcactaatc taattgatta 36780tttagttgaa actaaattta ttaaaagtaa atcagaagca agaagattaa ttagtcaaaa 36840aggtttgaca attaacaata aacacgtttt agacttaaac caaataattg aatgaaaaga 36900agagttacaa attattagaa aaggtaaaaa aagtttttta acaattaaaa ctgttaattc 36960ttaggataaa gaaagtgcaa taaacttaat taagcaattt attaatggaa aaaattagaa 37020cacgttatgc accatcccca acaggatatc tgcatgttgg tggtacaaga acagcaatct 37080ttaacttttt actagccaag cactttaatg gtgagtttat tatcaggata gaagatactg 37140atactgaaag aaacataaaa gaaggaatta attcacaatt tgataacttg cgttggcttg 37200gagtcattgc agatgaatcg gtttataacc ctggcaatta tggtccatat ctgcaatcac 37260aaaaactagc agtttataaa aaactagcat ttgatttaat tgaaaaaaat ctggcatatc 37320gttgcttctg tagcaaagaa aaattagagt cagatagaaa acaagccatt aataaccaca 37380aaacccctaa atacttaggt cattgtcgta atttacattc caagaaaatt actaatcact 37440tagaaaaaaa tgatcctttt actatccgct taaaaataaa caatgaagct gaatatagtt 37500gaaatgatct ggttagggga caaattacta ttcccggcag tgcgttaaca gatatagtta 37560ttcttaaagc taatggtgtt gctacttata actttgcagt tgttattgat gattatgata 37620tggaaattac tgatgtttta aggggagctg agcacatctc taacactgca taccaacttg 37680ctatatatca agcattaggt tttaaaagaa ttccccgctt tggtcatctt tcagttattg 37740ttgatgaaag tggcaaaaaa ctttctaaac gtgatgagaa aactactcag tttattgagc 37800agtttaaaca acaaggctat ctacctgaag cattattaaa tttcttagca ctcttaggtt 37860gacatccaca gtacaaccag gagtttttta atttgaaaca gttaattgaa aactttagtt 37920taagtagagt tgttagtgct cctgcttttt ttgatattaa aaagctgcaa tgaatcaatg 37980ctaattacat taaacaatta actgataatg cttatttcaa tttcattgat aattacttgg 38040atgttaaggt tgattattta aaagataaaa acagggaaat aagtttactt tttaaaaatc 38100aaataaccca tggtgttcaa ataaacgaat tgataagaga atcttttgcc actaaaatag 38160gtgttgaaaa cttagctaag aaaagtcata ttttgtttaa aaacatcaaa ctttttttag 38220aacagcttgc caaatcttta caagggttgg aagaatgaaa agctgagcaa attaaaacaa 38280ctattaacaa agtaggagca gtgtttaact taaaaggtaa acaacttttt atgccaataa 38340ggttaatttt tacaaataag gagcatggac ctgatttagc acatattatt gaaatttttg 38400ataaagaaag tgcaataaac ttaattaagc aatttattaa tgcaacaaac cttttttaa 38459 47400 DNA M. genitalium 4 aggaaaatta aaattaagtt agcactagta gatacaaaagatgaagttat acaaagttct 60 taacagtaaa acaactgata aaagtctttg tttggaagttgagattgatc caaattactg 120 acaagctacc caaaaaaaac tagtaggtga aatggctaaatcgataaaaa ttaagggttt 180 tcgtcccggt aaaatccccc ctaatttagc cagtcagtcgattaataaag ctgaattaat 240 gcaaaaaagt gcccaaaacg tcatgaacag tatttatgaatcagttcaac aagaagagat 300 cgttgctagt aatgataatg tcattgatga ttatcctaccattgatttca aaacgatcac 360 tgaacaaaac tgtgtacttt tgttttactt tgatctgatccctaactttc aactccctga 420 ttacaaaaag ataaaagatt taacaccact taccaagttaactgaagctg aatttaacaa 480 cgaaattgaa aagctggcaa aaactaaaag cacaatggtagatgttagtg ataaaaaact 540 agctaatggt gatattgcta tcattgattt cactgggatagttgataaca aaaaactagc 600 atcagcttca gcacaaaact atgaattgac aattggttcaaatagcttta ttaagggttt 660 tgaaaccggg ttaatagcaa tgaaagttaa ccagaaaaaaactttagcac taacttttcc 720 tagtgattat catgttaagg agttgcaatc aaaaccagttacatttgaag tagttttaaa 780 agcaattaaa aaactggaat tcaccccaat ggatgaaactaatttcaaat cctttctccc 840 tgaacaattc caaagcttta cttctctaaa ggcatttaagagttattttc ataagctaat 900 ggaaaacaaa aaacaagaga caattctcca ggagaataaccaaaaaattc gtcagttctt 960 acttactaat accaaacttc cttttcttcc agaagcgttaattaaactag aagctaaccg 1020 cttgttaaag ctccagcaaa gccaagctga acaatataaaatcccctttg aaaaactctt 1080 aagtgcttct aatatcaccc taacagagtt acaagatcgcaacataaaag aagctaagga 1140 aaatgttacc tttgctttgg taatgaaaaa gatagctgacattgaaaaga ttaaggttga 1200 taataacaag attaaagctg aaattgaaaa tgttattgctgttgaatatc cctttgctag 1260 tgatgaaatg aaaaaacaac tcttttttaa tatggaacaacaaaaggagt ttgtggaatc 1320 aattatcatc aacagattaa caacaactaa aatcgttagctattcaactc attagcactc 1380 aaagcttgtg agtgctaaga aatgtgttaa aatttattgaaattccctaa ttaactttta 1440 aatatgcccg ttacgaagaa aagtcagatc ttagtagttagaggtcaagt catttttcct 1500 tttgttccct ttagtttgga tgttggcagg ccccgttcgcgtaagatcat caaagcgctt 1560 aaaactctga aaaccaaacg tttggtttta gtaacccaaaagtttactgg tgaacaaaac 1620 cctgagttta atgacatcta tcatgtcggt acactctgtgagattgatga gatagttgat 1680 gttccagggg ttgatagtaa aacagtagac taccgtattaaaggcagagg tttacaacgg 1740 gttttaattg aaaaattctc agatgcagat attaatgaagttagttacca attacttaac 1800 tccacagtta aagatgaagc taatgttgac aggttcttacagcgaatctt tcctgaaaaa 1860 gaagaaattg aacagttaat ggaaggagct gagaagtttttagaacttga aaacatcagc 1920 aaaacagtta atgttcctaa gggtttaaag caacttgatattatcacctt taaactggct 1980 aatcttgtcc ctaacactga aagtattaaa caagctatcttagaggaaaa tgagatagca 2040 aaccgattgg aaaagattat ccaagcaggg attgaagatttacagaagat ccaagattat 2100 ggtagatcta aaaacaagga aactgagttt gataaacttgacagtaaaat tacccgcaaa 2160 attaacgaac aactctcaag acaacaacgt gatttctatcttcgtgaaaa gctaagaatt 2220 atccgtgaag agatagggat tagttccaaa aaagaggatgaagttgctag tattagaaag 2280 aaactggatg aaaaccctta ccctgaagcc attaaaaaacggattttaag tgaacttgaa 2340 cactatgaaa actcttcctc ctcttcccaa gaatcaaccttaaccaaaac ttacattgat 2400 acgcttttaa acctgccttg atgacaaaag agcaaagataacagtgatgt taaaaactta 2460 attaagacgt tagataaaaa ccacactggt ttagataaggttaaagaaag gattgttgag 2520 tatttagcag tacaactaag aacccaaaaa aacaaaggtcctattatgtg tttagtaggt 2580 cctcctgggg ttggtaaatc aagtctagct aagtctattgcagaagcatt agataagaag 2640 tttgtcaaga tctcattagg gggagtacat gatgaatcggaaatcagagg tcaccgtaaa 2700 acttacttag gttctatgcc aggaaggatt ttgaaagggatgacccgtgc taaggtaatt 2760 aatcccctct ttttacttga tgaaattgat aagatgacctcctccaacca aggttatcct 2820 tcaggtgctt tacttgaagt attagatcca gagttaaataataagtttag tgataactat 2880 gttgaagaag attatgatct ttctaaagta atgtttatcgctactgcaaa ctacatagaa 2940 gatatccctg aagctttact tgataggatg gagataattgaactcacttc ctatacagaa 3000 caagagaaga ttgagatagc aaaaaaccac ttaattaagcgttgccttga ggatgctgat 3060 cttaacagtg aagaattgaa gttcactgat gaagcaatcagctacatcat taagttttac 3120 acaagagaag cgggggttag acaattagaa cgattaatccaacaagttgt aagaaagtac 3180 atagtagcaa tgcaaaaaga tggcatcaaa caagaaacgattgatgtaaa cgctgttaaa 3240 aaatacctta agaaggagat ctttgatcac actatgcgtgatgaagtgtc tctacctgga 3300 attgtcaacg ggatggcata caccccaact ggaggggacttacttcccat agaagttacc 3360 catgttgctg gtaaaggaga gttgatctta actggtaatttaaagcaaac aatgcgagaa 3420 agcgctaatg ttgctttagg ctatgtaaaa gctaatgcagagcgttttaa cattaatcct 3480 agtttgttta aaaagattga tattaacatc catgttccaggtgggggaat tcctaaggat 3540 ggacctagtg ctggtgctgc tttggtaact gcaatcatctcatcattaac tggtaagaaa 3600 gtagatccta cagtggctat gacaggagag atcactttaagaggcaaagt gttggttatt 3660 ggtggggtga aagaaaaaac tatctcagct taccgcggtggggttacaac tatctttatg 3720 cctgagaaaa acgagcgcta tttagatgaa gtacccaaagagatagtaga taaacttaac 3780 attatctttg ttaaggaata cagtgatatc tacaacaagcttttcagtta gttttatata 3840 atttttgcat taaaaggagt gagcaattaa aatgaatattaatttcacac ctgctggtga 3900 aaatcgtaat tttttgcaag aaattggtcg taatattaacgatgaagtat taaaaaataa 3960 ggtcgatcct attattggaa gagataacga aattcgtcgtttaattgaga tattaagtcg 4020 taaaagcaaa aacaatcctg ttttaattgg tgaacctggagttggtaaaa ccgcaatagt 4080 agaaggtttt gttagaagag ttgttagtaa tgatgtacctttaaatttaa gggatgtaga 4140 aatttatgaa ctatctcttt ctggattaat tgctggcactaaattccaag gtgaatttga 4200 aaaaagaatt aataccattc ttaagcaagt aaaagaatcaaatggcagga ttattctttt 4260 tattgatgaa attcaccaaa tagttggatt aggacgtaattctagcagtg gtgcaatgga 4320 tattgccaat atattaaagc cgatgctagc tcgaggagaaataaaagtaa ttggcgctac 4380 tactctaaaa gaataccggg aatacattga aaaagatggcgctttagaac gtagatttca 4440 aaaaattctt attaacgagc ctagtagtca agaggcactaacaattatgc gtggtttaaa 4500 aacacgttga gaactctttc ataacatcac tatttttgatagtgctttag tagctgctgt 4560 tgaaatgtca actcgttata ttaatgaacg taatttacctgataaagcca ttgatcttat 4620 tgatgaggct gctgctaaga tcaaaacaga aatgtcatctgaaccagttg caatagatag 4680 tcttaaacgt gaaataatca atcttgagac agagtatgcagctcttaaac aagataagga 4740 aaatgataac aaacaatcaa agaaagaata tttagagaaactaaaaaaac aattagatgc 4800 tcttaaacaa aagcgtgatt cacttataaa tgaatgaaaaaaggaaaagg ctgattttga 4860 aaacattaat aagctcaaaa aagagattga agaatttcaaaccaaactag agacatacca 4920 aagtgaagga aattatgaaa gtgcatctaa aattctgtactctgatatcc caagacttaa 4980 aaaagaactg gaaagtgcac aacaaaaata tgcaacttctaagcacgatt tatttaaaac 5040 tgaagtttct gaaaatgaaa ttgctgaagt tatttcacaaacaacaggaa ttccacttaa 5100 aaaactatta gaaagtgaaa aggataaact tttgcacttaggtgatgaaa tcaaaaaaag 5160 agttaaagga caagatgaag ccatcgatgc tgttgttaacactgtaatta gaggtagagt 5220 aaatataaat gacccaaaca aacctattgg ttctttcatctttttaggtt ctactggtgt 5280 tggtaaaact gaacttgcca aatcattagc agaagttctttttgacaatg aaaaagctct 5340 gattcgtttt gatatgagtg aatatatgga aaaacattcagtagctaaat taattggtgc 5400 acccccaggg tacataggtt atgaacaatc aggtttgctaactgaagcgg ttagaagaaa 5460 accttatagc gtcttgttat ttgatgaaat tgaaaaggcacatcctgatg taactaatgt 5520 tttattacaa gttttagatg atggtacttt aaaagattcacaaggaaggg ttgttaattt 5580 caaaaatact ttgataatta tgacttctaa cctaggttcaaattttcttt tagaaggaaa 5640 aaaagatttg gccattcaaa gtctaaagaa acatttccgtcctgaattta taaatcgtat 5700 tgatgagata gtatttttca atgttcttga gaaagatacagttttatcga taatcaacag 5760 cttgttggca caactttcaa aacgcttgaa taaacaaaatttatttttta attttgattc 5820 aaatctaaca gagtttatct ataaaagtag ttttgatcaacagtttggtg caagaccaat 5880 taagcgcttt attgatcata gtgttgcaac tttaatagctaaatatatcc ttcagggaaa 5940 gataaaaaaa ggtgttggat acaacattgc agttgttaaagacaatatta ccattacaca 6000 aaataataag tcttaaaaag ataactcctt ttcagaataataaatagaga tatagaatga 6060 gaataaataa accttttagt gatgatagca acacagttgtttttgtgagt tcaaaaacat 6120 atggtgtaaa agaagaagct gcacataatc ctaatgttgaatttggtgtt gttttaccaa 6180 ctgattttcc tgctttcaac cgtgctttag ttcaatttcttaaaagaaag aaaaccaaat 6240 taaacattaa tcttgacagt cttatagaac tttataagaaaaatgaaaat agtggttgtt 6300 ttcatactgc gataaaaact gttattacaa gtgttactttttgtgaaact actcctttca 6360 caatgaaaac caaacctgaa aaaaatgttg aagttgctgttcaatgtgct gttgaatatc 6420 acaacttagt taaagaatat gaaacagtag gcgaatatgttaacctagca agagaattac 6480 aagacactcc ttcagatcta ctttattcag aagtatttgttaaacatttt gaaaaggctg 6540 caagtaaatt gcctgtaaaa ataaaagttc ttaaacaatcagatctaatt aagaaaaaaa 6600 tgggtttact tttaggggtt aatcaaggct ctgaaagagaagcacgttta cttgttatta 6660 gttatcaagc taataaaaat tccaaagaaa aacttgcttttgtagggaaa ggaattactt 6720 atgattcagg cggaatgaac attaaaacag gtgattatatgcgtggcatg aaatatgaca 6780 tgagtggtgc ggctatagta tgttctactg ttttggcattagctaaaaac aaggttaaaa 6840 ccaatgttgt tgcagtagca gctcttactg aaaatcttcctggtgctaag gcgcaacgtc 6900 ctgatgacat taagatagca tacaatggta aaagtgttgaaatagataac actgatgctg 6960 aaggaagatt ggttttagct gatgctatta catatgctgctaaggattta gctgctacac 7020 atattattga tgtagcaacc cttactggtt taatgtcatacatattgagt actacctata 7080 caggtatttt cagtacttgt gatcaccagt gagaatcttttaaaaaagca gcatgtagtg 7140 caggtgaacc tgtatgaaga ttacctatgc accctgattatttaaaacct ttacagctaa 7200 caaaacttgc tgatttgcaa aattctacta gtgcaagaggtgctggatct tcaagagcag 7260 cttgtttcct tgcagaattt agagaaggtg tatctttgatccattgtgat attgcatcaa 7320 ctgcttccat tgagaacctt ggacaaggtg ttttagtgagaaccttgtac gaacgtgcta 7380 gtcagcttgc aaataaataa 7400 5 11138 DNA M.genitalium 5 atttaaaacc agaaaataca ttaaatatcc taagtaattt atggcagaaatgatagaagc 60 aaaaaatctt cgtaatgggc aaaccatctt cggtcctaac aaagagattttattagtact 120 ggaaaataca tttaacaaaa ccgcaatgcg ccagggaatt gttaaaactaaagttaaaaa 180 cttaagaact ggggctattg tttggcttga atttactggt gacaaattagaacaagtaat 240 tattgataag aaaaaaatga atttcttata caaagatggt aataactttgtttttatgga 300 tcaaaaagac tacagtcaga ttgagattaa tgaaaaaaaa ttagagtgggaaaaaaattt 360 cattactgaa gaaattgaag ttactgttat tacttatcaa gatgaaattctaggagttaa 420 tttacctgat ttagttccta ttgaagttga gtttgctgaa gatgctattcagggcaatac 480 tgctaacatg gcaagaaaaa aagcacgcct tgtaactggt tatgaacttgatgtacccca 540 atttattaat actggtgata agattgtaat tgccactgtt gatggcaattaccgtgaaag 600 gtttaacaaa taataacaaa gcctttgccc acatgcgttg gtagttatttattatgtcaa 660 gaacagttga tttaaaaaac ttccgtaact ttggcattat ggcccatattgatgctggga 720 aaaccaccac atcagaacgt attttgttcc attcaggtag aattcacaagattggtgaaa 780 cccatgatgg tgaatcagtg atggactgga tggaacaaga aaaagaaaggggtattacta 840 tcacctctgc agccacttca gtgagctgaa aaaactgcag cttaaacttgattgacactc 900 ctggccatgt tgactttaca gttgaagtgg agcgtagctt aagggttttggatggagcaa 960 ttgcggtatt ggatgctcaa atgggagtag aaccacaaac tgaaacagtatgaagacaag 1020 cttcacgcta tgaagtacca cgggtaatct ttgttaataa gatggataaaaccggtgcta 1080 actttgagcg ctctgtttta tcaattcaac aacgcttggg agtgaaagctgttcctattc 1140 aatttcccat aggtgctgaa aatgatttca atggcatcat tgatatcatcactaaaaaag 1200 cttatttttt tgatggtaat aaagaggaaa atgctattga aaaaccaattcctgaacagt 1260 atgttgatca agttgaaaaa ctttacaaca acttagttga agaagttgctagtttagatg 1320 atcaactcat ggctgattat ctagatggta aaccaattga aattgatgcaattaaaaatg 1380 caattagaaa cggggtaatt cactgtaagt ttttcccggt attgtgtggttcagcattta 1440 aaaacaaggg aattaaactc ttacttgatg cagtggttga ttttctcccttcacctgttg 1500 atgtcccacc tgctaaagca attgatgcaa acaacaaaga gatatctattaaagctagtg 1560 atgatgctaa ctttattggc ttagcattta aagttgctac tgatccttttgttggtagat 1620 taacttttat tagggtttat gcaggagttt taaaatctgg ttcttatgttaagaatgtta 1680 gaaaaaacaa aaaggaaagg gtatcacgtt tagtgaaaat gcacgcacaaaatcgcaatg 1740 aaattgatga aattagagca ggggatatct gtgcagtaat tggcttgaaagatactacta 1800 ctggagaaac tttaactgat gataagcttg atgtgcaact agaagcaatgcaatttgctg 1860 aaccagtgat ctctttagca gtagaaccta aaactaaagc agatcaggaaaagatgtcaa 1920 ttgctttatc aaaactagca gaagaagatc ctacttttaa aacctttagtgatcctgaaa 1980 cagggcaaac tattattgct ggaatgggtg agttacacct tgatatcttagttgatagga 2040 tgaaacgtga atttaaggta gaagttaaca ttggtgcacc tcaagttagctttcgtgaaa 2100 cctttaaatc aactagtgaa gttgagggta aatacatcaa acaatcaggtggtagaggtc 2160 aatatggaca tgttaaaatc cgttttgaac ctaataaaga taagggctttgaatttgttg 2220 ataagattgt gggcggaagg attccaaggg aatatattaa accagttcaaactggtcttg 2280 aaaatgcaat gaattcaggt cctttagcag gttacccaat gattgatattaaagctacct 2340 tatttgatgg ttctttccat gaagttgact caagtgaaat ggcttttaaaattgctgcat 2400 ccttagcttt aaaagaagca ggtaaacaat gtaacccagt tttacttgaacctattatgg 2460 caatagaagt tactgtacct gaacagtact ttggggatac aatgggtgatatcagttcaa 2520 gaagagggat cattgaaggt actgaacaac gtgataatgt tcaactaataaaagcaaaag 2580 tacctttaaa agagatgttt ggttatgcca ctgatttacg ctctttttcccaaggtaggg 2640 gtaattatgt aatgcaattt agccattatg ctgaaactcc taaaagcgttgttaatgaga 2700 taattgctaa taaaaaatag cagttgttct ttgaaatgat ctaataaggctttaacaagg 2760 gtgcttttgc caacaccgct aggaccagta atgacaaaaa ttctcccctgattgttcact 2820 tcaattgtta gaataatttt aactttactg tttttatcaa tgacttttcaaccaactaaa 2880 acttggcttg tttttgatga taatgctttg attaacaagc caactgaagctgttaatttt 2940 ccaatagatg agcaaattga aacctgtatt aaaaagatga ttgcatatgttgatgcttca 3000 tatgatggta aagcacaaga atatgacatt attccaggaa ttgggatagctgctaaccag 3060 attggctatt gaaaacaact gttttacatc cacctcaatg atttaaacaaagaaaaaaag 3120 tgcctactga tcaatcctaa aattattgat caaagtgaaa ataaagcatttttagaaagt 3180 ggtgaggggt gtttaagtgt taaaaagcag cacaaaggtt atgtaattcgtagtgaatgg 3240 atcactatta aaggttatga ttggtttgaa aaaaaagaga ttaccattaaagcaactgga 3300 ctatttggaa tgtgtttaca gcatgaattt gatcacttac agggacgctttttttaccaa 3360 agaattaacc ctttgaatcc atggtttaaa aaaccagaat gaaaagtgattaatcctact 3420 ttgaagacaa gtaatggata acttactgca atgattaccg ccttacaacaattagcacaa 3480 gatgaaaaaa aatagagctt tcaatcaggt taaaaaaaca aagtttgacggtaggattaa 3540 aaccagtgcc aaacaccagt tacgtaatgt taaaaccggg gttaaagatggtgtttttat 3600 ctataaaggt cctttaactg ttagtgagtt tgcaagtaaa actaatatcgctgttgctaa 3660 cattatcaaa cacttttttt taaatggttt ggcactaaca gttaattcagttttaacaaa 3720 tgaacagtta gcagatgcat gtgttaactt tgggtttgac tttaagatggaaactgaagt 3780 tacccatgaa aatattgtag ctaacatcca gtttgaagat agtgatgatttattgcaacc 3840 aagaccacct attgttacta tcatgggtca tgttgaccat ggtaaaacttcgcttttaga 3900 cacaattaga aaaactaatg taactgctaa ggagtttggc ggaattacccaaaaaattgg 3960 tgcttatcag gtgaaaaatc accaaaataa aacgattact tttattgatactcctgggca 4020 tgaagcattt actttaatgc gtgcaagggg tgcaaaagta actgatattgtggtgttggt 4080 tgtggcagcg gatgatggga ttaaaaagca aacagaggaa gcaattagccatgctaagag 4140 tgctaacact cctatcattg tttttattaa caagatggat aaaccaactgctaaccctga 4200 tctggtgatc caacaactca ataagtttga tttagttcct gaggcttggggtgggaaaac 4260 tatctttgta atgggtagtg ctttaactgg tcaagggatt aatgagttgcttgataatat 4320 cttgttgcta ggggaagtgg agggttatca agctaactat aatgcccattcatctggtta 4380 tgcaattgaa gtacaaactt caaagggact tggccctatt gccaatgtcattgtaaaaag 4440 gggtacttta aagttaggtg acattgtggt gttagggcct gcatatggaagagttagaac 4500 gatgcatgat gaaaatggta atagcttaaa acaagcaacc ccttcaaaacctgtgcagat 4560 ctcagggttt gacattatgc ctgttgctgg ggaaaagttc attgtttttgatgatgagaa 4620 ggatgcaaag ttaattgcta acaagtttaa agaacaacaa aaacaaaaagctaacaactt 4680 aacagttaat caaaccttaa aagaacagat taaaaacaag gaaattaagatattaaattt 4740 gatctttaaa gcagatagtg atggttcatt gcaagctatt aaacaagcagttgaaaacat 4800 taatgttgct aagatctcac ttagtatcat ccatgctgca gtggggcagatatcagagag 4860 tgatattatg ctagcaaaag catcaggggc tttattgttt agtttaaacttaggtttgag 4920 tcaaactgta aaaaacattg ctagtttaca aggggtaaaa ttagaagttcactaccatat 4980 ccctaaacta gcagaggaga ttgaaaacat cttaaaaggt caattagatcctgtttatga 5040 agagattgaa ataggtaaag cggaagtttt acaactctgg ttccactctaaaatcggtaa 5100 tattgcagga accattgtta aatcaggaaa gataaaaaga gggaatttatgtaagttatt 5160 cagagataaa gagattatct ttgaaggcag aattgactct ttaaaaaatgaaaaaacgcc 5220 tgttaattta atagaaacag ggaagaattg tgggatagtt attaatggttgcaatgatat 5280 taagattggt gatatcattg ttgcttatga aaagcagata gttaaagatggcaagctata 5340 gaaaacaacg gattgaaaat gatatcatcc gcttaattaa tcgcacgattattaatgaga 5400 tctatgatcc tgttgttaag ttaggtcatg ttagccatgt gaagttatcagctgattttt 5460 ttcatgcagt agtttatctt gattgttatg atcgtagtca gattcaaactgtagttaatg 5520 cttttaaaaa ggctcagggc gtttttagtc aaatgttagc acaaaatttgtacctagcta 5580 aaagtgtaaa actccacttt gtgaaggatg atgcaattga caatgctttgaaaatagaac 5640 agataattaa ctctttgaaa aactaaaaga acaactcaag acaatcaaacaatttattag 5700 ataaagatga tctatctcaa atctgcaaat gaagttgcag ggattaaaaaagcatgtgca 5760 atcttcaaag cagttaaggc atattttaca attgaaaagt tacttggcaaaaagttggtt 5820 accattgatc gtttaatcaa acaattcatt gaacaaaaac aagctaaatgtgcgtttcat 5880 ggttatctag gtttccctgg ttttaactgt ctatcgttaa accaaacggttatccatgga 5940 gttgccgatc aaactgtttt taaagatagt gataaactaa cgcttgacattgggatagac 6000 tatcatggtt atctttgtga tgcagctttc actttacttg gtaataaagctgatccaaag 6060 gcagtaaaac tgttaaatga tgttgaacaa gcatttagta aggtaattgaacctgagcta 6120 tttgttaaca atccgattgg taatttatcc aatgcgatcc aaacttactttgaaaacaag 6180 ggctattttc ttgtcaaaga gtttgggggt catggttgtg ggattaagatccatgaagat 6240 cctttaatct taaactgggg agagaaaaac cagggcgtta ggttacaagaggggatggta 6300 atctgtattg aaccgatggt tatgactgat agtagtgaga taacaatggcagctaacaac 6360 tggaatgtac taactttaaa gagtaagttt aactgtcatg tggaacagatgtatcacatc 6420 acaaacaacg gctttgaatg tttaactaac taatgaaaaa cgataaactctttctaacag 6480 gtaagatact ggaaattatc catggtgata agtaccgggt gatgcttgaaaacaatgttg 6540 aggttgatgc acatctagca ggtaaaatga agatgaaaag aaccaagattctccctgggg 6600 atgttgttga ggtggaattt tctccctatg atttgaaact aggtaggataacccaaagaa 6660 aataatttaa ttgatgaaaa cagtactaat ttagggatag ttaagatggaaaacgcttta 6720 aagttagcac aagaaaaaca gttagatcta gttctaattg ctccaaacccaaccaaaccg 6780 atcgttaagt tgttggactt tggcagatat acctatgatt taaagcgtaagaaaagacaa 6840 gccaagaaaa accaaacaat catccaaacc aaagaagttg ttgtcaaaccaacgattgct 6900 aaacatgatt tagaatttag agcaaaacag agtaagaatt ggatagaaaaaggtcatcat 6960 gtcaagttta tagtccgtgc ctttggcagg gttagcacca ggatagagttaattgaaaag 7020 gtgtttgatg acttttacca gttagttaaa gatgtagttg agatccaaaaacctttaacc 7080 gcttcttcca aaacgatgta cgctgctcta ttagtacctt taaaaagatagtgaatatat 7140 taatatttat tggtctttgt caaaaaataa gatgcaacta aaaaagccccattttcaacc 7200 aaataaaatt gctaattgta ttgtgatcgg gggaatgatt gctttaggaaaaaccaccat 7260 tgctaataca ttagctaacc acattcaagc tgcaaaagtt gtttgtgaattggaaactaa 7320 tgaccagttg gttgaacttt tactagcaaa gatgtatgaa cgtagtgatgaattgctcta 7380 ttcacctttg tttcagcttt attttacgct taatcgcttt ggtaaataccagaacaattg 7440 caacactatc aatccaacca tttttgatcg ttctatcttt gaagactggttgtttgctaa 7500 gcacaacatc attcgtcctg cagtcttttc atactataac caactgtgaaatagattagc 7560 aaaagaacta gttaataagc atggggttcc taatttatat gtcattttggatggggattg 7620 aaaattattt gaaaaaagac tatttatgcg taaccgcaaa gtagagattgataactttac 7680 taaaaatcaa ctttactttc aaaatttaca cagggtttac actggatttatggaagcggt 7740 ttgtaatgat tttgggatta attactgtat tatagatgca aaactaccaatagtaactat 7800 tattaaaatg atccttgaaa aattaaagtt acaaaagtta gattgaaaatttatctaaat 7860 taaataataa aagtgttttt gctgctttta attttgtcat ggaactaaataaaaattacc 7920 taactcaaga aggatttaag caactggaaa aagaacttga aaacctaatccaagttaaac 7980 gtcctgagat tatcagactc ttacaagaag cacgtgatca gggtgatttaagtgaaaatg 8040 ctgattatga tgcagctaaa gcacagcaag gtgagattga aactaggattgctgaaattc 8100 aagatatatt agccaacgct aagttaatta gtgaccacca agcaaaaaccaaagtaacaa 8160 aagttagctt agggagcact gttgagatct atgattacag ttctaaatcgaacgaaaaat 8220 acacaattgt aggtacactt gaagcaaatc ctgaagaaca caaaatttccaatgaatcac 8280 cccttgccct tgcaatctat gggcgtttaa ttggtgatga atgtgatgttgttggtattg 8340 aagttcccta tcgtgttaaa atcctgaaga tcagcaacag ataatatttactatcttatt 8400 agtaatatta agcttagtgc aataatggca acgaaaatag agctaataaaagaattgcgt 8460 aaatcaacac aagcaagtgt tatggattgt aaacaagctt tggaaaaaaataatgatgat 8520 tttgagaaag ctgttaagtg attaagagaa aatggcattg ttaaatcaaccaaaaaatta 8580 aataaggttg caagtgaagg aattattgtt ttaaaaagca atttacacaaggcaattatg 8640 gttgagataa actcacaaac tgattttgta gccaaaaatc aagagttaaaagaattttca 8700 gatttaatgc ttgaaaaaat atttgaaaaa gtaaatccaa aaacagaattagttgaaatt 8760 gaaaaaattc aaattaataa tgatgaaaaa gttagtgaaa aactagcattaattgcttct 8820 aaaactgatg agaaaatagt acttagaaga gtagttgtat ttgaaactaaaactaatcaa 8880 attttcacct atttacatgc caataaaaga attggggtaa ttattgagattcaaggaaaa 8940 ctcaacgaag atgatggtaa gcatttagca atgcatattg ctgctaattcaccacaattt 9000 attgatcaaa gtgatgttaa tcaaacatga cttcaaaatg aaagaaatattatccgttcc 9060 caagcagaat tagaggttaa agaaaatcct aaaaaagcaa tttttttagaaaaaactatt 9120 gaaggtagag ttaacaaatt actaattgat acctgcttaa ttaaccaaaaatacttaatt 9180 gatgaaacta aaacaattgg tcaattttta aaagaaaaac aagctaaggttcttaaattt 9240 attaggtatg aagtgggaga ggggattata aaggaaactg ttgattttgttagtgaagta 9300 aatgcacaaa tcaaacaata agggattata aaggaaactg ttgattttgttagtgaagta 9360 aatgacaaaa gcacattaca ttgatttttt taaacaagca gctgataaaaaaattcaatg 9420 attaaaagaa gagttaacaa agattagaac aggtaggcca aatcctaaaatctttgataa 9480 tcttttgatt gaaagttatg gacaaaaaat gcctttaata tctttagctcaagtgactat 9540 taatccgcca agagaaataa tcataaaacc atttgatcct aagagtaatactaatgctat 9600 ttacagtgaa attcagcggg caaacattgg tgttcaacca gttattgatggtgaaaaaat 9660 tcgtgttaat tttccccaaa ttactcaaga aactcgctta gaaaatattaagcacgttaa 9720 aaaaataata gagcaaattt atcaagaact gagggttgta agaagagatgcattacaaat 9780 gattaaaaaa gataatcaca atgaggattt agaaaactct ttaaaagctgaaatagaaaa 9840 aattaacaaa aattattcta atcaattaga agagattcaa aaagacaaagaaaaagaatt 9900 gctaacaatt taaatcttaa acttatttaa aattaacaac ataatttaaacaaatggcaa 9960 gagagaaatt tgaccgttcc aaaccacatg tcaatgttgg taccattggtcacattgacc 10020 atggtaaaac cactttaaca gctgctatct gtacagtttt agcaaaggaaggaaaatcag 10080 ctgcaacgcg ttatgatgaa attgataaag cccctgaaga aaaagcaaggggaatcacaa 10140 ttaactctgc acacgtagaa tattcttctg acaaacgtca ctatgcccatgttgactgtc 10200 ctggacatgc tgactacatt aaaaatatga tcacaggtgc tgcacaaatggatggagcta 10260 ttctagttgt ttcagcaact gatagtgtga tgccccaaac ccgcgagcacatcttacttg 10320 cccgccaagt aggggttcct aaaatggtag tttttctaaa caagtgtgatattgctagtg 10380 atgaagaggt acaagaactt gttgctgaag aagtacgtga tctgttaacttcctatggtt 10440 ttgatggtaa gaacactcct attatttatg gctcagcttt aaaagcattggaaggtgatc 10500 caaagtggga ggctaagatc catgatttga ttaaagcagt tgatgaatggattccaactc 10560 ctacacgtga agtagataaa cctttcttat tagcaattga agatacgatgaccattactg 10620 gtagaggtac agttgttaca ggaagagttg aaagaggtga actcaaagtaggtcaagaag 10680 ttgaaattgt tggtttaaaa ccaattagaa aagcagttgt tactggaattgaaatgttca 10740 aaaaggaact tgattcagca atggctggtg acaatgctgg ggtattattacgtggtgttg 10800 aacgtaaaga agttgaaaga ggtcaagttt tagcaaaacc aggctctattaaaccgcaca 10860 agaaatttaa agctgagatc tatgctttaa agaaagaaga aggtggtagacacactggtt 10920 ttttaaacgg ttaccgtcct caattctatt tccgtaccac tgatgtaactggttctattg 10980 ctttagctga aaatactgaa atggttctac ctggtgataa tgcttctattactgttgagt 11040 taattgctcc tatcgcttgt gaaaaaggta gtaagttctc aattcgtgaaggtggtagaa 11100 ctgtaggggc aggcactgta acagaagttc tagaatag 11138 6 23272DNA M. genitalium 6 tttacagttt tagcaataat aaaaaatctt tgaatattgcatgaaaaaaa taaacgttgt 60 ttacaatcca gcatttaatc caattagctc taaattaaatcaaactcaac ttttaaaaaa 120 tgctagtgaa gagttagata tagaactaaa attctttactagttttgata ttaatacaac 180 taaagcaaaa gcaaatttac ccttcatatc caacaaaattctttttatgg ataaaaatat 240 tgctttagct agatgactag aaagcaatgg ttttgaagtaattaacagtt caattggaat 300 taacaatgca gataataaag gacttagtca cgctatcattgcacaatatc cattcataaa 360 gcagattaaa acacttttag gacctcaaaa ttttgacagggagtgaaatc cagtaatgct 420 cgatgttttt attaatcaaa taaaacaaag tatggagtttcctgttattg ttaaaagtgt 480 ttttggttct tttggtgatt atgttttttt gtgtttagatgaacaaaaat taagaaaaac 540 tttaatgtct tttaatcaac aagcaattgt gcaaaaatacattacttgct ctaaaggtga 600 atcggtaaga gttattgttg tgaacaataa agttataggtgctttacata caactaataa 660 tagtgatttt cgttctaatc tcaataaagg ggcaaaggcagaacgctttt ttttgaataa 720 ggaacaagaa aatttagcag ttaaaattag taaagtaatgcaactttttt attgcggtat 780 tgattttttg tttgatcaag acagatcatt gatcttttgtgaagtaaatc ctaatgtgca 840 attaacaaga agctcaatgt atttaaatac taatcttgcaattgagcttt taaaagcaat 900 ttagtattat tgcagtttta ctgcataatg taaaattacacagcatgtca gatacaaata 960 ctgaaaaacc tgagttagtt tcccttaata agttaagtgagatgcgcact aacatcggga 1020 tggttaaacg ttattgaaac ccaaagatgg gattctttatcgaacctgaa cgtaagcata 1080 ataacgattt attgaagctt gatctacagt accaagcgttaaaaactgct tataacttca 1140 ttaaggatgt tgttaaaaat cacggacaaa tcctttttgttggaacaaag aatgattatg 1200 ttaaaaaact ggtaattgat attgctaaaa gagttaatgttgcatatatt acccagcgct 1260 gattaggtgg tactttaact aactttaaaa ccctttctatctcaattaac aaactcaata 1320 aattagttga acagcaaaag caaaatgcaa atgatctaaccaagaaagaa aacctgttac 1380 tttcaagaga gattgaaaga cttgaaaagt tctttggtggggtcaaaaat ttaaaaagac 1440 ttcctaatct aatagttata gatgatcctg tttatgaaaaaaatgcagtt ttagaagcaa 1500 acagcttaaa aatccctgtt gtggcactat gcaacaccaacaccaatcca gagctagttg 1560 actttattat tccagctaat aaccaccaac cccaaagtacttgtttattg atgaatttac 1620 tagcagatgc gatagcagaa gcgaagggtt ttgaaaccttgtatgcttac aaaccagatg 1680 aacagatcca aattgaaatt cctcccaaac aagaacgccaagttattaac cgttccaata 1740 ccagaaacat cactaaccag cgcttaaaca ttaaccgtcaacaacaagaa actttataga 1800 tggctaaaaa aacagttaaa tgtgggagct aattaagcgtttgtaccaca gcaaaatatg 1860 gctaaaaaaa cagttacaag aatcgctaag attaacctaattggcggaca agcaaaacct 1920 ggccctgcgc ttgcttctgt agggattaat atgggtgagtttaccaaaca atttaatgaa 1980 aaaaccaagg atagacaagg tgaaacgatc ccttgtataatcactgcttt taacgataaa 2040 tcatttactt ttgtcttaaa aactacccct gttagtaacttaattaaaca agctgctaaa 2100 ctagaaaaag gtgctaaaaa tgcaaaaact attgttggaaaaatctcctt acaacaagct 2160 aaggagattg cgcaatacaa gttagttgat cttaatgctaacacagttga agcagcatta 2220 aaaatggtgt taggtacagc taaacagatg ggaatagaggtaactgatta atgaaaaaac 2280 tatcaaaaag gatgcaagct gttaccaagc tcattgataaaaacaaactt tatcctatcc 2340 aagaagcatt tgaattaatt aaaaaaacag caattactaagtttgtcagt tcagttgata 2400 ttgctgttag tttaaacctt gatactacta aagctgaacaacagttaaga ggtgcaattg 2460 cttttccttt tagtattggt aaatctatca gaattttagctatcactgat gatgagaaaa 2520 aagctagtga agcaggtgct gattttgttg gtgggcttgataagatagaa gcgataaaaa 2580 atggctgatt agattttgat ctaattatca cttctcccaagttcatggga gcattaggta 2640 aactaggaaa actattagga accaggggat tgatgccaaacccaaaaact gaaacagtta 2700 ctgatgatgt agttagtgct attaaagctt ataaaaagggtaagaaagaa tatcgaactg 2760 attcatttgg caacatccac ctctctttag gtaaaacagataccaaaact gagcacttgg 2820 ttgctaatgc catggcttta atagatttaa ttaagtctaaacgtcctagc acagtcaaag 2880 gtacttacat taaaaatatt gctttgacaa caacaatgggaccaagttta aaagtaaagc 2940 tacctgatta aacaaccagc tagattttgt tagaatacttcagttgtcta tatggctaca 3000 atagcgcaat taattagaaa accacgccaa aaaaagaaggttaaatcaaa gtcacctgca 3060 ctccattata acctcaacct tttaaacaaa aaaactaccaatgtttactc accactaaag 3120 cgtggtgttt gcaccagggt tggcaccatg acccccagaaaacctaattc tgcactaaga 3180 aagtatgcta aggttagact tacaaatggc tttgaagtacttgcttatat cccaggagaa 3240 ggtcataacc tacaagaaca cagtgttact ttattaagggggggtagagt aaaagatctc 3300 cctggagtta gataccatat tgttcgtggt actttagatacagttggtgt tgacaaaaga 3360 agacaacaac gttctgcata tggcgctaaa aaaccaaaaccaaaatctta acttgatcag 3420 ttaaataatg agaaaaaatc gtgctttaaa aagaactgttttacccgatc ctgtttttaa 3480 caacacactg gttacaagga ttattaatgt catcatgaaagatggcaaga agggtttagc 3540 acaacgcatc ttgtatggtg cttttgagat cattgaaaaacgcaccaacc aacaaccttt 3600 aactgtcttt gaaaaagcag ttgataatgt tatgccccgcttagagttaa aagtgagaag 3660 aattgctggt tctaactacc aagtaccaac tgaagttccccctgacagaa ggattgcttt 3720 agcactaaga tggattgtga tctttgctaa caaaagaaatgaaaaaacaa tgcttgaacg 3780 tgttgctaat gaaattattg atgcttttaa taacacgggtgctagtgtta aaaagaagga 3840 tgatactcac aagatggcag aagctaacaa agcctttgcccacatgcgtt ggtagaaata 3900 taactttact caatgagttt ttccaaaaag tttttatgcactacaatatc attcttttag 3960 ttgatggtac gcttagttta gaacaagcta accaagttgaacaaaaacac caaaaattgc 4020 ttgaaaaggc aactgaattt aaaagtgaat acttaggtttaaaagagttg gcttacccca 4080 ttaaaaagca actttctgct cactattaca gatggagttttcatggtgaa agcaattgta 4140 ctaaggagtt taaaagagct gctaacatca ataagcagataataagagag ttaattatta 4200 acagagaaaa agactatggt tatttaggtt cagttaaccctaaaaaacaa caactgtctt 4260 tgcagaagct aaccaagtat aatgagatta ttgctagtgaaaataatcct gataacccag 4320 atgcgcctgt cacttctggt ctagcttctg ttaaaccacggctatcaaga gttgaaaaac 4380 aaaaggaacg tgaacttgaa aagtgaacgg ttgttcaccaatcaggtaac tttgatactg 4440 tacagatcaa tccttatcgt cctaggataa aacgctttttacaaaacaac caacaaacct 4500 cccaagctaa taataaccaa cctcgttttc aaaatcaatttaaaaaagga gcaaaacctt 4560 agacccctat atttgaaaat gatgtccaac tagaggaggaaagtgatgat taataaagaa 4620 caggatttaa accaattaga aaccaaccaa gaacagagtgttgaacaaaa ccaaactgat 4680 gaaaagcgca agccaaaacc aaactttaaa agagcaaaaaaatattgtcg attttgcgcc 4740 ataggtcaac taaggattga ttttattgat gatttggaagcaatcaaacg ctttctcagt 4800 ccctatgcaa agattaatcc tagaagaatt acaggtaattgcaacatgca ccaacgtcat 4860 gtagctaatg ctctaaaacg agcacgttac ctagctttagtgccatttat taaagattaa 4920 atatgaagat aattttgaag caagatgttg ctaaattaggcaagcggttt gatgttgttg 4980 aagttaaaga tgggtttgct atccattttt tatttcccaaaaaactagct gcacctttaa 5040 caaagaaagc aattgctaac cgtgatttgt ttttaaaacaacaacaagaa caataccaaa 5100 aaaatcgtgc cttagctgaa aaattgaaac tagtaattgaacaaacacca ttaacttttc 5160 aactcaaaca acacgatggc aagccatatg gttcaatcatcaccaaacaa ataattaatt 5220 tagcaaaaca acaaagactt gatttacagc gctttatgtttaaagataat gtgcgcttac 5280 agtttggtga acacaaacta attttgcacc tttttgaggagataactgca actttaactg 5340 ttatagtgaa ccctgaaaat gggacaacaa actagccgtagtcaatttat taactaacta 5400 gtgaactaga ttttgatgaa tagcgctgta aaatatcctgagctgaagat caaacttgag 5460 tcttatgata gcaccctttt agatctcact attaaaaagatagttgaggt tgtaaagggt 5520 gtgaacatta agattaaagg tcctttacct ttgcctactaaaaaggaagt gatcaccatt 5580 atccgctctc cccatgttga taaagcatcc agagagcagtttgaaaaaaa tacccacaag 5640 cgcttaatga ttcttgttga tgttaatcaa ggagggattgatagtttaaa aaagattaag 5700 atcccagttg gggttacact gcgtttttca aaataggttatggatgtaag gggaatattt 5760 ggtgttaaag tagggatgag tcagatcttt actgagcaaaatgagtgctt acctatcacc 5820 attgtttatt gtgaagctaa tcaggtggct gggattaaaacgattgctaa agataattac 5880 aacgccactc tattaagctt tcaaactgtt gatgaaaaacaacttaacaa acctaaacaa 5940 gggttctttt ccaaacttaa actagaacct cataaatatctgagggaaat cagaaagatg 6000 caagggtttg agttaggtaa gaagatcacc ccccaggagttgtttaagat aggtgaatat 6060 gttgatgtca cttcactcac caaaggtagg ggttttacaggagcgattaa aaggtgaaac 6120 tttaagatag gtcctttggg tcatggggcg ggttatccccaccgctttca gggttctgtg 6180 caagcaggta gaggtggtag tagtgcgcag cgtgtttttaagggtaagaa gatgtctggg 6240 cattatggtc atgaacaagt tacgatccaa aacctctttattgttggctt tgatgaaatc 6300 aataagttag tgttagtttc aggcgcaatt gctggtcctgagggtgggat tgttttaatt 6360 aaaactgcaa aaaagaaaac tggcaagata aaagatataaagttagcagt acaaactgtt 6420 aaagccccac aactaaaagc accaaaaaag cagaaaactaaggttgaaac caaccaggtt 6480 aacccaaaaa ttgaagaaga gaaaactaag taatggctaaacttaaagta atccagtttg 6540 atggtagttt taaaggtgag atccaacctg ctaaccacctccttttaaaa aaagcagtga 6600 tccaaccagt gtttgatgct atcttattag aacaagcagcatgtagacaa ggcactcact 6660 ctactttaac taagggtgaa gttagtggtg ggggtaaaaaaccatataaa caaaagcaca 6720 ctggtaaagc tagacagggt tcaataagaa acccccattatgtggggggt ggtgttgttt 6780 ttggtcctaa acccaaccgt aactacaaac taaaactaaacaaaaaggct tatcaacttg 6840 ctttaactag tgcctttgca caaaagctta acaacaaccaagtgatagtt gctgaagcca 6900 agttgtttga acaaaccaat gccaaaacta aaaagatgctgacgtttctc aagaatgcca 6960 aactaactga gcaaaaactc ttgtttgtga ttgatactatctcaaaacca ctgttgttga 7020 gtactaacaa cctaaagcag atagtagtca aacagtttaataaagtatca gtaagagatc 7080 tacttttagc taaaactatc atcattgaaa aagctgcttttacaaaactg gaggaacgac 7140 ttaaataggc tatggatgta accaacatac tcttaaaaccagtcttaact gaaaagagtt 7200 atctcaacca gatgggggaa ttgaaaaaat atgtctttgcaattaaccct aaagctacta 7260 aaaccaaagt aaaactagcg tttgaaatta tctatggggttaaaccttta aagattaaca 7320 cgctaattag aaaaccagtg accattagaa atggcactaaataccctggg tttagtaagc 7380 tagcaaaact agcagtaatc accttaccta agggaatggatattgccatt actggtgaga 7440 aaacaaccaa gaaagaaaca aaggatcaat aatggcaattaaaaagatta ttagtcgttc 7500 taacagtggg attcacaacg ccactgtcat tgactttaaaaaactcctta ccaattccaa 7560 acccgaaaag tcgcttttag ttactttaaa aaaacatgcaggaagaaaca accagggcaa 7620 gatcactgtt cgccaccacg gtgggagaca taaacgtaagtaccgtttaa ttgattttaa 7680 gcgttaccac tatgacaatt taaaagcaac tgttaaatcgattgaatatg atcctaaccg 7740 cagttgtttt atctcccttt tacactatca gaatggggttaaaacttaca tcattagtcc 7800 tgatgggatt aaggttggtg atcaagttta ttcatctgatcatgccattg atatcaaact 7860 aggttattgt atgccccttg cttttatccc tgaaggaacccaagttcata acattgaact 7920 taaccctaag ggtgggggta agatagcaag aagtgctggaagttatgcga ggatcttggg 7980 tcaagatgag actggtaaat acatcattct ccagttaatctcaggggaaa ctaggaagtt 8040 tttaaaggag tgtagagcta cagttggtgt tgtctctaacttagatcata accttgttgt 8100 aattggtaaa gcagggagaa gtcgtcataa gggaatcagaccaacggtta gaggttcagc 8160 aatgaaccct aatgaccacc cgcatggggg tggggaagggagaagcccag ttggcagaga 8220 tgcaccaaga accccttggg gcaaacgcca tatgggtgtgaaaacacgta acatgaaaaa 8280 acattcaact aacctgatta ttagaaacag aaaaggagaacaatactaat gtcaagaagt 8340 agtaaaaagg gcgcatttgt tgatgctcac ctcttaaaaaaagtgattga aatgaacaaa 8400 caagccaaga aaaaaccaat taagacttgg tcaagaagaagtactatctt ccctgagttt 8460 gtgggtaaca ccttcagtgt gcataacggt aaaacctttattaatgttta tgttactgat 8520 gatatggtag gtcataagtt gggtgagttt tccccaactagaaactttaa acaacacact 8580 gctaaccgtt agttatgatt gcttttgcta aacaatacagagttcacatc tccccccaaa 8640 aagcacggtt agtgtgccag ttaattgtgg gtaagaagattaatgatgcg caaaacatcc 8700 ttttaaatac gccaaagaaa gctgcttact ttttaactaagttactaaat agtgcgatta 8760 gtaatgccac taataaccac gggatgagcg gggatcttttgtatgtattt gaatgtgttg 8820 ctaaccaagg acctagcatg aaaagaacaa tcgctagagccaaaggttca gggagtgttt 8880 taaccaagcg ttcttcaaac ctagttatta agttatctgataatcccaat gaaagaaaat 8940 tactcttaac ccaacaaaag gaactggtga aaaaaagaacaatgggtcat aaaaaagaga 9000 aagcaaagca aaagcaaaaa caacaataac tatgggacaaaaagtaaatt caaacggctt 9060 aaggtttggc attaataaga actggatctc acggtgaactgccagttcca accaacaaac 9120 agcaacctga ttagtacaag atgagaagat ccgtaacctcttttttatca actatcgcaa 9180 cgctcaggtg tctaatgttg agatagaaag aacccaaacgactgttgatg tttatgtcta 9240 tgcagctcaa cctgctttat tgataggcag tgaaaacaaaaacatccaaa agattaccaa 9300 aatgatccaa atcattgtgg gcagaaagat taaacttgatcttactatca atgagatcgg 9360 ctctccgatg ttatcaagta ggatcattgc ccgtgatattgctaatgcga ttgaaaacag 9420 agtaccactc cgttcagcaa tgcgccaagc tctaaccaaggttttaaaag caggtgctaa 9480 tgggattaag gtattggtat caggcagatt aaatggggcggaaattgccc gtgacaagat 9540 gtatattgag ggcaatatgc ctctttcaac tttaagagcagatattgact atgcctttga 9600 aaaagcaaaa accacctatg gcattattgg ggtgaaagtatggattaaca gggggatgat 9660 ctatgcaaag ggtttaaaca gaaccccagc acacatcctccatccccaaa agaaacagct 9720 aaaaacccca actatcaaaa aaaccaattc agtaatagcaaaacaaaaac tcactggtag 9780 tgatattgaa actgctagtt taaaagcact tactgataataatcaaaacc acgaatagtt 9840 aagatgttac aaccaaaaag aaccaaatac agaaaaccacataacgtcag ttatgaagga 9900 cacactaagg gcaatggtta tgttgctttt ggtgagtatggaattgttgc tactaagggt 9960 aattggatcg atgcgagagc aattgaatca gcgcgggttgctatctcaaa gtgcttgggt 10020 aaaactggaa agatgtgaat caggatcttc ccccacatgtcaaaaaccaa aaaaccctta 10080 gaagtgagga tgggttcagg gaaaggtaac cctgaattttgggttgctgt tgttaaaaag 10140 gggacagtga tgtttgaagt tgctaacatc cctgaacaacagatgatcaa agccttaaca 10200 agagcaggcc ataaactccc tgttacctga aaactaatgaaaagagagga gaacagttaa 10260 tgacaatcgc taaggagctg aagcaaaaga gcaacgaagagttagtgaaa ctagtaatta 10320 agcttaaggg tgaactctta gaataccgct ttaaacttgcccatggtgaa cttgacaaac 10380 cccatctgat tgccaaggtg agaaagttat tagcagttgtacttactatt ctcactgaac 10440 gcaaactcaa ctgacaagtt gaaaaagata agtacaagttactttcaaga aaaaccaatg 10500 aacttattgt taacagttga aagcaaaaac tatcaactaaacctgaatcc aaacaagaaa 10560 ctaaaaaggc tgaagttaaa cctaaggttg aatcaaagcctgaatccaaa caagaaacta 10620 aaaaggctga agttaaacct ttaaaacaag aaactaaaaaagttgaagtt aaacctaaag 10680 ttgaaccaaa acctttaaaa caagaaacta aaaaggttgaagctaggatt gaaactaaga 10740 ctaaagttga atcaaaacct ttaaaacaag aagttaaaaaggttgaagct aaaaaatctg 10800 tttcaaaacc ccaaaaacca gttaaagcca aaatgattaaaacaaaggag aaaaaacaat 10860 aatgaagcgc aaccaacgta agcagttaat tggcacagttgttagcacca aaaatgctaa 10920 aacagcaact gtcaaagtaa catcacgctt taaacatcctttgtatcaca aatcagttat 10980 tcgccataaa aagtaccatg tccataactt tggtgaacttgttgctaatg atggtgatag 11040 ggtacaaatt attgaaacaa gacccctttc cgctttaaagcggtgaagga ttgtcaaaat 11100 cattgaaaga gcaaaatagt ttatggttag ttttatgacaagattaaatg tagctgataa 11160 tacaggcgct aagcaagtag gtattatcaa agttttaggtgctacataca aacgttatgc 11220 attccttggt gatgttgttg ttgtatcagt taaagatgcaatccctaatg gcatggttaa 11280 aaagggtcaa gtgttaagag cagtcattgt tagaaccaaaaagggacaac aacgccaaga 11340 tggtacccac ctaaagttcc atgacaatgc ttgtgtgcttatcaaagaag ataaatcccc 11400 aaggggaaca agaatctttg gaccagttgc tagagagttgagagaaaaag gttacaacaa 11460 gattttaagc ttggcggtgg aggttgttta atgcaaaggattagaaaagg tgataaggta 11520 gttgtgatca ctggtaaaaa caagggtggt agtgggatagtgcttaaggt attaaccaag 11580 caaaacaaag cgattgttga ggggatcaat aaggttactgttcacaaaaa agaacaagtc 11640 aacaagcgca gcaaacaaac aaacccaact actaaagaagcccctttacc attaaataaa 11700 cttgctttat ttgatcagaa ggccaaacag caaacaattggcaagatcaa ataccaaatt 11760 gatcctaaaa ccaaacaaaa aacaagagtc tttaagaagactaataatgc catttaactg 11820 ttatgaataa ccttgaaaaa acctataaaa ctgagttagttaatcaactc caacaacagt 11880 tgggcttttc ttccattatg caagtcccta agttaacaaaaatcgttgtt aacatgggag 11940 ttggggatgc aattagagac aacaagttcc ttgaatcagcactaaatgaa ctgcacctga 12000 ttactggtca aaaacccgtt gctactaaag ctaagaatgctatctcaact tacaagttac 12060 gtgctggcca attaattggt tgtaaagtta ctctaagaaataaaaagatg tgatcctttc 12120 tggaaaaatt aatctatatt gctctgccca gagtaagggactttcgcggt ttatcactgc 12180 gctcttttga tgggaaaggt aactatacga ttggcattaaagaacagatt atcttccctg 12240 aaattgtcta tgatgatatc aaaagaatta ggggttttgacatcactatt gtcacttcca 12300 ccaacaaaga tagtgaagca cttgctttac tgagagcactaaagatgccg tttgtaaaag 12360 aatagatatg gctaaaaaat cattaaaagt aaaacaatcccgtcccaata agtttagtgt 12420 acgcgactac accaggtgtt taaggtgtgg gcgtgctagagcagtgttaa gccactttgg 12480 tgtgtgtagg ttgtgtttcc gtgaacttgc ttatgcaggagcaatcccag gagttaaaaa 12540 agcatcatga taatcaataa agttcccaaa gcccattttgatccagtttc tgatcttttc 12600 actaagatca acaatgctag aaaagctaag cttttaactgttaccaccat cgcttctaag 12660 ttaaagatag ctatcttaga gattttgatt aaagagggctatttagctaa ctatcaggtg 12720 ttggaaaata aaactaaaac caaaaaacta gttagtttcacattaaaata cacccaaaga 12780 aggatatgtt ctattaatgg ggtgaaacag atctcaaaaccaggattaag aatctatcgt 12840 tcctttgaaa aacttcccct tgttttaaat ggtcttggtattgcaattat ctccactagt 12900 gatggagtga tgactgataa agtagcaagg ttaaagaagattggtgggga gattttagct 12960 tacgtttggt aaaaaattat gtcaaaaata ggaaatagatcaatcaaaat tgatcctagt 13020 aaagtgagtt taatgcaaac aacaacactg cttactattaaaggaccatt aggggaaaac 13080 accattaaac tacccaaaaa cttaccctta aagtttgttgttgaaaatga cactattaaa 13140 gtaactaata acaacaactt aaaacaaact aagatcttacacggtacttt caatgcgtta 13200 gttaacaacg cagttattgg ggttaccaag ggttttgaaaagaaactcat cctagttggg 13260 gttggttatc gtgctaatgt ggaagggcaa tttctcaacttacaattggg ctattcccat 13320 cctattaagg agttgatccc aaaccaactt actgttaaagtagagaagaa cactgaaatc 13380 accattagtg gaataaaaaa agagttagta ggtcagtttgccactgaaat cagaaagtga 13440 agaaaacctg agccttataa gggtaaaggg gtactttactttaacgaagt aattgttaga 13500 aaacaaggta aaactgcaga gggcaagaaa taagatgacaagaaacgata aaagaaggat 13560 tagacacaaa cggattgtca aaaagattag gttaactaaccttaacaaca gggttgtact 13620 aattgttatc aagagtttaa aaaacatctc ggttcaagcttgggacttta gtaagaacgt 13680 tgttttaaca tcaagttcct cacttcaact aaaattaaaaaatggcaaca aggagaatgc 13740 taaactagtg ggaatggata ttgcaaccaa actcatcaaactaaaccaaa aggatgtggt 13800 ttttgatact gggggtagta agtaccatgg taggattgctgctttagcag aaggagcgcg 13860 agctaagggt ttaaattttt aaagctatga atgatcaaaaaactactaac actggcttgt 13920 taacttccac tcttaaaacc aagcccaaac acaaccttaaaccttccagt gaagccatta 13980 aaaaagcagt gtccaaaaag gaaggtcatt acaaaaacaagcgctttcaa aaacataact 14040 ttaataacaa aagtgagttt gaagagagga ttgtcaaactcaaacggatc tccaaaacca 14100 caaaaggtgg gagaaacatg cgctttagtg tccttgttgttgttggtaac aaaaagggca 14160 aggttggtta tgggattgct aaggcattgg aagtaccacttgccattaaa aaagcgatta 14220 aaaaagccca taactccatt catacagtag agatccataagggttcaatc taccacgaag 14280 tgattggtag aaaaggtgca tctaaggtgt tgttaaaacctgcaccttta ggaactggga 14340 tcattgctgg gggagcgatc cgtgcaattg tagagttagctggttttagt gatatctata 14400 ccaagaactt gggaagaaac acccccatta acatgatccatgccactatg gatgggatct 14460 taaagcaact ctcacccaaa aaagtggcat tattaagaaataaaccaatt agtgatctat 14520 aaaaacaatg gaactacacc aattaaaaag tgtctctaaaagccgtaacc acaagtccaa 14580 agtggtaggt aggggccatg gctcgggatt aggtaaaacatcatcacgtg gtcaaaaggg 14640 acaaaaagca agaaaatcag gtttaactag gttaggttttgaagggggac aaacacccct 14700 ttaccgccgg ttgcctaagt atggggttgc taacaaagggatcttaaaaa aaaggtgggt 14760 tgttttaaat ttgaacaaag ttgctaaact caatctcaaaacagttacta gagcaacttt 14820 gattgaaaaa aaggtaatta gtaaaaaaaa taacctccctttgaagttaa ttgggaacac 14880 aaaactcact actcccatcc actttgaagt gcaaaaaatctccaaaaatg ctttaaatgc 14940 agtgcaaact agcaaaggta gtgtgaaaat tatcacctaaaaactaggta ggataaccca 15000 aagaaaataa ttaaaatatt atgaaggtta gagcaagcgtaaaaccaatt tgtaaagatt 15060 gtaagatcat caaacgtcac cgcatcttaa gggtgatctgcaaaaccaaa aaacacaagc 15120 aaaggcaagg ataatggcac gaatcttagg gattgatatccccaaccaaa aacggatcga 15180 gatagcttta acatacatct ttgggattgg tttgtcaagtgcaaaaacaa tcttaaaaaa 15240 agcaaagatt aaccctgata aacgcgttaa agatctgagtgaagaggaac ttgttgcgat 15300 tagaaacgca gcaagcggtt acaagattga gggtgatttgagaagagaga ttgctttaaa 15360 catcaaacac ctaacagaga tcggttcttg aaaagggattagacacagaa aaaacctgcc 15420 agtaagagga caacgcacta gaaccaacgc aagaaccagaaaaggcccta gaaaaacagt 15480 ggctaacaag aaaattgaaa gtaagtaatg gctaagaaaaaaaagattaa tgttcccagt 15540 ggtttgatcc atgtctcctg ttcacctaac aataccatagtatcagccac tgatcccagt 15600 ggtaatgtct tgtgctgagc gagcagtggt acagtaggattcaaaggttt tagaaagaaa 15660 accccttact cagcaggggt agcagctgat aaggtggctaaaactgtgaa agagatggga 15720 atggggagtg ttaagatgta tctgaaggga acaggtagaggaaaagacac cacgattaga 15780 agctttgcta atgctgggat tacgatcaca gaaatcaatgaaaaaacccc tattccccac 15840 aatggctgca agctcctaag cgtccgcgct aatcaaaacaacaacttatg gaaaaatttt 15900 taaagagtta ggtttaaaat tccgttctta ataaaatagagctatgtcat acattaataa 15960 agaggggaaa accacagctt gaagagtgat gacagtgcgtcagcaagtga gtgcagtgtt 16020 aagttatgga aagattcaaa ccactttaaa aaaagctaagaacacccaaa aaaggttaga 16080 gaagattatt accattgcta aagttgataa ctttaacaaccgcagggctg ttaaaaagtg 16140 gttattaaat accaattcat tagatgtaga tcaactcacaaaccaccttt ttaaaaaagt 16200 agcaccacgt tttttaaagc gtaatggtgg ttatagtagagtgttaaagt tgggagttag 16260 aaggggtgat agtactgaaa tggcgatctt acagctgatagatgctacca actaacgatg 16320 tacgctgctc tattagtacc tttaaaaaga tagttatgaaaaccaaaagt gctgcagtaa 16380 aacgctttaa actcaccaaa tcaggacaaa ttaagcgcaaacacgcttat acttcccacc 16440 tcgcgcccca caaatcaacc aaacaaaagc gccatttgcgcaagcaagct actgtgagca 16500 acagtgaatt gaaaagaatt ggtattttaa tttagttatgcgtgttaagg gaacaaatac 16560 aaccaggatt agaagaaaaa aatggttaaa acaagctagtggtagctttg ggacaagaaa 16620 agcttctttt aaggcagcta aacaaactgt tatccaagcaagcaagtatg cttaccgtga 16680 taggagacag aaaaaacgtg agtttcgttc gttgtggatcttaaggttaa atgctgcact 16740 gcgtgcacaa gggatgactt attcagtgtt tatcaatgaattgaaaaaag ccaagatagt 16800 cattaacaga aaggtacttt ctgaactagc aattaaagaacctaataagt taaatctgat 16860 tatcaatacc atcaaaaaac caactaataa accaactgttgcaaaaactt agatgacctt 16920 ttgcaactag aaagttttgg gagatattaa tcttaatcatggataaagcg taccactttt 16980 agtttggtgt agggttgacg gtggccataa cgcttgaggtggtgtttttg ggagatgtgt 17040 ttaattagtt taattttcga ttttaaaccg tgtttttcaatcacacaaac aaccttagct 17100 ttttcaaggt aaggtttgcc tatcttttca tcaagcatcaataccttatc aagttggatc 17160 tcctgaccaa ctttaccagc taatttttca acaaaaatagactcgttttc atggactaaa 17220 tactgcttag caccacaaac cacaatagca tgcatttaggcatttagttg gtgtttgatg 17280 atgttaaccc gggttttgct ttgtttacta ccaaacttttgaaagcggac aatgccatcg 17340 ctcaaagcaa agagggtgtt atcactaccc attgcaacattttgtcctgc aaagatctta 17400 gttccccttt gtctatagat aatctgacca actctaatcatctgaccatc tgccttctta 17460 gcgcccaagc gcttagaatg tgaatcacgt ccattcttagtggaaccaac cccttttttg 17520 gaagcgaaaa actgtaagtt aatttggtag cagtaactgtttttactcat tgttgttaat 17580 tttaaataag tttaagataa gctggagata atgcttataatcttcaagga cttaaattta 17640 gtgaaaacaa acaattgcca aattattggc tgatgaaaacaactttcctt accacaaaag 17700 acattcttaa gtttcattcc cttatttttg gtcactagtgcttttgtttt aactggaatt 17760 gttgaaagtc ttttaacatt tggaactatt attgaacaaattgataaatt cactgatcag 17820 actaatgtga tgttattaat ttatgcagtt atctacacttttaatccaaa aagttgattg 17880 ttaaaaaacc aacaattctt tttaagtgca ttagcttatatattatttac ttttattggc 17940 tataacctaa ttttgtcaat agctggtata gcttataaatcaacaaatcc atataagtta 18000 acaagtagta tttttctcca tgtaattgca ccaatagcattcttcatagc aagttttatc 18060 aaaataaaac atgagaaaga tgtcaatatt aacatgttctttaaaagcct attattattc 18120 atgatctatc ctttaatata tgggctttat ttagtaactattccatatgt aaggcattat 18180 ctttttaatg gtaggccatc tacttatacc atttatggcagcattacaaa tactaaaaat 18240 aatccttttg cttgattagt tgtatttgca gttttatttatctatttccc cttgagttac 18300 ttagctatat atctattaca acttaagtta ataaaaaaagccatacaacc gcaatttaat 18360 ttgcctttta cattaaataa atgaaaacaa aaataatgaatatattaata tttattggtc 18420 tttgtcaaaa aataagatga aaaaggcaat ccactttcagagtcaaccag ttgtttttaa 18480 ctgtgcttca tgcaatagca actttaccat tgactccactgccaaacaaa aggatcttgc 18540 cattgacatt tgtggaaaat gtcatccttt ttacatagggcaattaacca aacaaaccgt 18600 gcatggacgg gctgaaaaac tttctcaaaa gttcaacgctggaaaggctt ttttagaaaa 18660 taaaactaaa aagagtaacc aagctaaagt tgaaaaacaaactaggcacc gttctattaa 18720 cgagctttag tttagccttg attattaaga taatttaaaatcgaaaacac atgaaatata 18780 ctggtagtat tttcaaacga tcaagacgtt taggtttttctttacttgaa aacaacaaag 18840 agttttccaa aggaaaaaaa cgtaaatcta ttcccggtcaacatggaaat aggtttcgtt 18900 cctcaacttt atcaggttat gcccaacaac tccaagaaaaacaaaggatg caatacatgt 18960 atggtattac tgataaacaa tttcgtaggt tatttcgctttgttttaaaa caaaaaggta 19020 acttaacagt taatttattt agagttttag aatcacgtttggataacata gtttacagaa 19080 tgggttttgc accaacaaga aagagtgcaa gacaaatggtaaaccacggt catgtgattt 19140 taaatgatca aactgttgac accccttcaa tcatcattaatcccggggat aaagtccgtt 19200 taaaagcaag aataactaaa tccccattag ttaaaaattttattgaaaac agtgttatct 19260 catcatttgt ggaaaccaac aaaaaggcat ttgaaggtacttatataaga ttcccagagc 19320 gtagcgaact acctgctgga ataaatgaat cttacgttgttgagtgatac aagcgtttag 19380 ttaaataatg tcgtaaggta gtattgcaca aagaggtaaaacgtaaatat tatttacgtt 19440 ttacctcttt gtgcaatact accttacgac aacgtgaacaaaacttatta agtgctagtt 19500 tttctggatt tttcttgacg tttttaaagg ttaaataattaatctcagaa cattcattac 19560 aacctagtcg tgtgcttctt ttaacagcca tggatttatcatcgtttgtg ctattgcgaa 19620 tattgtagtt aatggtagat agtaagaaaa ataaaaaacagcaggttacg gatttttcta 19680 atttactctc tcaaagtaaa ggatttgtta tttttgactattcaggaatg tctgctgttg 19740 atgcaacttt aatgagaaaa aagttgttta ataagggtagtaagataaaa attgttaaaa 19800 acaatatctt aagacgtgct ttaaaaacta gtaattttgaaggtgttgat gaatcggtca 19860 tcaaaggaaa aattgcagtt gctgttggta ttaacgagatcttagaaacc ttaaaagttg 19920 ttgatagtgt agttaaagaa aaagagttaa tgaaatttgtttgtggtcat tttgataacc 19980 gtatttttaa tagtgatgac ttacaaaaaa tagcaaaactccctggtaga aatgaacttt 20040 atggaatgtt tctttcagtt ctacaagcac cattacgaaaatttctctat gctcttcagg 20100 cagtaaggaa tgctaagtaa attaaataaa tagaaaaatattatgggaaa actagataaa 20160 aaacaattaa ttgaatctct aaaagagatg actatagttgaaattgatga aataatcaag 20220 gctgttgaag aagcatttgg tgtaactgca actccaatagtagctgctgg cgcagctggt 20280 gctacacaag aagctgctag cgaagttagt gtaaaggtaacaggatatgc tgataatgct 20340 aagttagctg ttttaaaact ttatcgtgaa attactggagttggtttaat ggaagctaaa 20400 actgcagttg aaaaattacc ttgcgttgta aaacaagatattaaaccaga agaagcagaa 20460 gaacttaaaa agcgttttgt tgaagttggt gcaactgttgaagttaaata aagatggcag 20520 tacaacaacg gcgttctagt aaacaccgtc gtgataaaagacgttctcac gatgcactta 20580 ctctacaaac tttaagtgtt tgtaagaaat gtggtaagaagaagttatca catcgtgtgt 20640 gctcttgtgg tatgtacggt gaactaagag ttaaaaaagctcactaatca agataataat 20700 atactctaaa actaattaat aacctaaatg gctaatattaaatctaacga aaaacgatta 20760 cgtcaagaca ttaagagaaa tttaaataat aaaggacaaaaaactaaact aaaaactaat 20820 gttaaaaaat ttaataaaga gattaattta gataatctcagttctgttta ttctcaagca 20880 gatcgtttag ccagaaaagg gattatttct ttaaacagagctaagcgttt aaaatcaaaa 20940 aatgctgtta ttttgcataa aagtaataca aattcaactgcaaaaaaaca ataataataa 21000 tattaaaata gaatgcggtt ttgtatctaa atatatgcaaaaaacatcga tgcttacaaa 21060 ggaagaagcc attaaaaaca ggaagtggta tcttgttgacgctagtggtt tggttttagg 21120 caaattagca gttaaagctg caaatttaat tagaggaaaaaataaagcta attttactcc 21180 taatcaagat tgtggagatc atctaataat tattaacagtgatcaagtgg ttttaactgg 21240 aaataaaaaa gacaatgagt tttgatatca tcactctcaatacatgggtg gaattaaaaa 21300 aactagtgga agggatatga taaacaaaaa ttcagataaacttgttttca atgctgttaa 21360 gggaatgtta cctgataatc gtttaagcag aagattaataactaaagtac atgtttttaa 21420 gaatgataag cacaacatgg aagcacaaaa accaacattacttaattgaa gttaaaagat 21480 atggataaaa aatcttttta tggacttggt cgtcgtaaatcttctactgc taaagtttat 21540 ttatatcaaa gcaaagataa gggtaaaata accattaatcatcgtaatcc tagcgattat 21600 tttccaaata aattggtgat tcaagatatg gaacaacccttagagttaac caaacttaag 21660 gataactttg atatcaatgt tgttgttaaa ggtggaggatttactgggca ggcaggagcc 21720 attagattag gtattgttcg tgctttaata aaatttaatccagatcttaa aaagttatta 21780 aaaaccaaaa aattaacaac acgtgataag cgtgctaaggaacgcaaaaa atttggttta 21840 tatggtgcta gacgtgcacc acaatttact aagcgttaggttttctaatt ttgttataat 21900 tcaacgtgtt tattaattaa tgaaaattga taaagaacaaatcattaagg ctcatcaact 21960 tcacaaaaac gatgttggca gtgtgcaagt acaaatctctatattaacag atcagattaa 22020 aaaattaaca gaccacctgt tagcaaacaa aaaggattttatttctaagc gtggtttata 22080 tacaaaggta tcaaaaagaa aacggctact taaatatctaaaagaacgta atattgaaac 22140 ctaccgtgat ttgattaaaa atttaaacct ccggggttaatccatatatg cttatggatt 22200 aagtttaact taaatttaaa ttagaaacga ttttgttttttaagggtacg aattgtttta 22260 gttgaaacta gaatccgtgt tactttacca ttagtatctttaattttgca tgactgaagg 22320 tttacattcc attttcttct tgtaatagtt ttggaatgagaacgattatt gccatacaaa 22380 ggccctctta aggtaagttg gtcttttttt gccattacagacctgattta tacaaaaaat 22440 acttagaaaa taaaaatgaa aaaaataaat aaacaagcattaattgatgc agtagaacaa 22500 aaacagttaa aggaatatgt tcctgaattt ggagcaggagatgaagttaa tgttgctatt 22560 aagttacgtg aaaaagaaaa agttcgagtt caaaacttcactggaactgt tttaagaaga 22620 aggggaagag ggattagcga aactttcatg gtaagaaaaaccactgatgg aattcctatt 22680 gaaaaaaact ttcaaatcca caaccctaat atagacatagaagtaaaacg caggggtaaa 22740 gtaagaagag catacatctc ttatatgcgt gaaagatctggtaagtcagc aaaaattaaa 22800 gaaaaaaagt cttaaatgcg gatgggaaga gtacactatccgctttatag aatagtagcg 22860 gttgattcgc gagtaaagcg taatggaaag tatatcgctttaattggaca tctaaatcca 22920 gctttaaagg aaaataagtg taaattagat gaaactgttgccttagattg acttaataaa 22980 ggggcaattc caactgatac agtccgttct ttatttagtgaatctggttt gtggaagaaa 23040 tttattgaaa gtaaaaataa gaaagaaaca agtcctaaaaagtaggataa agaaagtgca 23100 ataaacttaa ttaagcaatt tattaatgaa acgaacataccaaccaagca aattaaagcg 23160 tgctaaaacc catggtttta tggctaggat ggcaactgcacaaggacgta aagttttaag 23220 gcaaagacgt tttaaaaatc gtgctcaact cacggtttccagtgagcgtt aa 23272 7 10809 DNA M. genitalium 7 tcgttttcaa aatcaatttaaaaaaggagc aaaaccttag atgcttaaag tgaatgctga 60 ttttttaact aaagatcaagttatctatga tttagtgata gtaggtgctg gccctgctgg 120 gattgctagt gccatttatggtaaacgtgc taacttaaat ttagcaatta ttgaaggaaa 180 cactccagga gggaagatagtaaaaactaa cattgtggaa aactatcctg gttttaaaac 240 cataactggt cctgaattaggtcttgagat gtacaaccac ttgttagcat ttgaaccagt 300 tgttttttat aacaacttaatcaaaattga tcatcttaac gatacattca tcttgtattt 360 agataacaaa acgacagtttttagcaaaac tgttatctat gcaacaggga tggaagagag 420 aaaacttggc attgaaaaggaagattattt ttatggtaaa gggattagtt attgtgctat 480 ttgtgatgcg gctctttacaaaggtaaaac agttggtgtt gtaggaggag gtaattctgc 540 aatacaggaa gcaatttatctttcaagtat tgctaaaaca gttcacctta ttcacagacg 600 tgaagtgttt agaagtgatgcattactagt tgaaaaatta aaaaaaatta gtaatgtagt 660 ttttcattta aatgctactgtaaaacagtt aataggtcaa gaaaagctcc aaactgttaa 720 attggcaagc acagttgataaatcagaaag tgaaattgca attgattgtc tctttcctta 780 cataggcttt gaaagtaataacaagccagt tttagatctt aagcttaatt tagatcaaaa 840 tggttttatt ttaggagatgaaaatatgca aactaacatt aagggttttt atgttgctgg 900 ggattgtaga agtaaatcattccggcaaat tgccactgca attagtgatg gggtaacagc 960 tgttttaaag gttagggatgacatttagta gattttatta gaattgtttc aactaataaa 1020 ttggccttat ggtaacagaaattagaagtc ttaaacaact tgaagagatc ttttcagcta 1080 agaaaaatgt tattgttgacttttgagcag catgatgtgg tccttgtaaa ctaaccagcc 1140 ctgagtttca aaaagcagcagatgaattta gtgatgctca gtttgttaag gttaatgttg 1200 atgatcatac tgatatagcagcagcttata acattacctc tttaccaact attgttgttt 1260 ttgaaaacgg ggttgaaaaaaagagagcca ttggctttat gccaaaaacc aaaattattg 1320 atcttttcaa taactaactctttgaaaaac taacagcttg aagtaaaatt aatcctaatg 1380 aaatcactct ttattggttattttgatgga ttacatcaag gtcatctatt tttaaagcag 1440 aacagtaagt ttgaaccaatggtgttatta attgataacc cacctttaaa acaaaccaac 1500 tggctttatg atttacaacaacgggttgca caaataaaaa cttacttgaa agcaactgta 1560 gaagtatttg atgttgccaaacataacatg aatgcactta gtttttttga acaacagatt 1620 aaaagattga attgtgatgaaattattgtt ggtacagatt ggcattttgg taatgatcat 1680 aaggatggga tctggttaaagaaactgttt aaaaatactg ttattgttaa taaaacaaac 1740 ctatcaagta gtgttatccgtaactatcta actaataatg aacttgaaaa agctaaccaa 1800 cttttagtgg aaccttattatagagtgggc acagtagtac atggtttaaa aaaggcaagg 1860 ttgcttggtt ttccaactgctaacattgtt atggataacc acttattgac tttaaataag 1920 gggagttata tagtaagagttttattaaat aaccaaactt tttatgggat tggttttatt 1980 agccaaaagg atcaggatttggtgtgtgaa acccatatct ttaactttaa taatgagatt 2040 tatggttcac tggtcaaatttacactgtta aagttcatta gaacaattag taagttttcc 2100 agtcaagcag ctttgcaaaaagcaattcaa agtgatgcta actttgcttt aaagtggttg 2160 gaaaaccaaa atttagataaaatttaatat ccttaaatag cttaaaaaat tactgcagct 2220 aagatatatg aaaaaagtgattgtgattgg aataaatcac gctggtacta gttttattag 2280 aactttactt tcaaaaagtaaggactttaa ggttaacgct tatgatagaa acacaaacat 2340 ctcgtttctg gggtgtggaattgcacttgc tgttagtggt gttgttaaaa acactgatga 2400 tcttttctat tccaaccctgaggagttgaa acagatgggc gctaacatct ttatgagtca 2460 tgatgttact aacattgatctaatcaaaaa acaggtaaca gttagagatt taacatcaaa 2520 taaagagttc actgatcagtttgatcaact agtaatcgct tcaggagcat gacctatatg 2580 tatgaatgtt gaaaacaaggtgacacacaa gcctttggag tttaactaca ctgacaaata 2640 ttgtggtaat gttaagaacttaattagctg taagttatac caacatgcac ttaccttaat 2700 cgatagtttt cgtaaagataaaaccattaa atcagttgct attgttggtt ctggttacat 2760 tggcttggaa cttgctgaagcagcttggtt atgcaaaaag caagtaacag taattgactt 2820 acttgataag cctgctggtaataactttga tcatgagttt actgatgaac ttgaaaaagt 2880 gatgcaaaaa gatgggttaaaactaatgat gggttgcagt gttaagggct ttgttgttga 2940 tagtacaaac aacgttgtcaaaggagttga aactgataag ggaatagtaa atgcagacct 3000 tgtgaaccaa tcaattgggtttagacctag cactaagttt gttcctaaag atcaaaactt 3060 tgagtttatt cacaacggttcaattaaagt taatgaattt ctccaagcac taaatcataa 3120 ggatgtttat gtcattgggggttgtgctgc tatttacaat gctgctagtg aacagtatga 3180 aaacatcgat cttgctaccaatgcagtaaa gagtggatta gtagctgcga tgcatatcat 3240 tggtagtaac caagttaaactccaatctat cgttggcacc aatgcactcc atatctttgg 3300 tttaaattta gcagcatgtggattaactga acagcgtgct aagaagttag gttttgatgt 3360 tggcatatca gttgttgatgacaatgatcg tcctgagttt atgggcagtt atgacaaggt 3420 gcgttttaaa cttgtatatgacaagaaaac cctaagaatt ttaggagcac aactcctttc 3480 ttggaatacc aatcacagtgagattatttt ctatattgca cttgcaatcc aaaagcagat 3540 gttactaact gaactgggtttagtggatgt ttattttctt ccacattaca acaaaccgtt 3600 taactttgtg ttagcaactgttttacaagc acttggtttt agctattaca ttcctaaaaa 3660 atagtatttt tttatcaatttaatatctaa atcgaaaaga aaacatgtcg ccacgggaga 3720 tagttttaaa agaaactaatcaaatagatt tcatttccaa tcaaagtatt tttgatatct 3780 caccaattag cggttgaaaaccatttgccc ctactgatca aattcttggt atttttattg 3840 tttttgtact gcttctaactttttttattt tttataagct taagttaaaa aaagcagatt 3900 ctttaaaaaa taattcatattttttgcttt tatttcaaat gttgtttgtt tgggtacaag 3960 atacaacagc agatcttttaggagaggaaa ataagaaatt tgctccctac tttttaatgt 4020 tgcttctgta catagtatcaagcaacttag ttagcttgct tggtggtatt tcaccaccaa 4080 catcatcttt aacatttactttttctttag gacttgcaac ttttattggg attgttgtta 4140 tggggattag ataccaaagatgaaattttt ttaaagagtt tgcctttgga attactgtta 4200 aaggaaaaaa gtattctactttcattccaa atccttttag tatattgagt ggatttgcac 4260 cgcttttttc tatttcattaaggttatggg gaaacatatt agcgggcaca gttattttgg 4320 cgctttttta taacttttgaatttttattt tttcaagtat taataaccaa ccattagcac 4380 ttagcttagg aacagtttttgcaggtttaa taaccccagt attacacatc tattttgatg 4440 taattgcagg tgtattgcagggttatgttt ttgtaatgtt gacttataat tattgggcta 4500 aaatgcgcaa tcaaggtttggaaaataata atgcaagtga attacacttt aaaggcataa 4560 aggtaattca agaaaatatttagttatgga acatgttaat gaaattttag ctacagttgg 4620 tgttatatta caacaaactcaaactaccca ggatgttaac gctagtgcta agctaggtgc 4680 ttatataggt gctggtgttactatgattgc aggttcaact gtagggattg gacaaggtta 4740 tatttttggt aaagctgttgaggcaatagc aagaaatcct gaagttgaaa aacaggtttt 4800 taaactaatt ttcattggttctgctgtttc tgaatctaca gcaatttatg gacttttaat 4860 ttcctttatc ttaatttttgtagcaggagc ttaaggatgg taaaggcaaa aaaacttgtc 4920 tttaaatgaa gcttattagtttttagcttt tttacactca gcttattttt ggtttcttgt 4980 actgagaatg ttagagaaattaagagtagt tcagtaataa atgaactttt tcctaacttt 5040 tgggtattta ttactcatttactagcattt ttcatcttac taacactgat gattttcttg 5100 ttttgaaaac caactcaaaggtttttaaat aaccgtaaaa atttactaga agcacaaatc 5160 aaacaagcta atgaattagaaaaacaagca agaaatctac ttgaagaatc taatcaaagg 5220 catgaaaaag cactaatagtttctaaagaa attgttgatc aagctaacta tgaagctttg 5280 caattaaaaa gtgaaatagaaaaaacagca aatcgccaag ctaacttaat gatttttcaa 5340 gctcgtcagg aaattgaaaaagaaagacgt tctcttaaag aacaatctat taaagagagt 5400 gtggaattgg ctatgttggctgcacaagaa ctaattctca agaaaataga tcaaaaatca 5460 gatagagaat ttattgataagtttattaga gatttagaag ctaacgaaac agaagatgat 5520 taatgcacaa gcatttggaactgcactttt tcaattaagt gaagagcaaa aacaagtaaa 5580 gaaaatttat gaagagtgccatttttttct gaaattaatg cgtaatttta aagatggttc 5640 attatcgttc ttacttaattcttatacact aacaaaacca gataaaataa gacttgttga 5700 taagttgttt aaaaatcatttttgtcaagt ttttgttgat tttttaaaag taattatttt 5760 aaagggttac tttactttagttgaacaggc aattaagtat ttttttgata atgttgaaag 5820 tcaaaaacac attcaatttatcaaaataat tactgctttt gaattaagct caaaacaact 5880 taacaaaatt attgcaataatggaaaaacg ttttaaaaca aaggttgttt ataaaactga 5940 gattgatcgc agtttaatttcaggaattag gatagaatca agttcccatt tatttgaaaa 6000 aaatgtgcgt gatgaattaaaacgcataat ggcccatttt atttaagtta attgagaagt 6060 tatggcagat aaactaaatgaatacgtagc attaatcaaa actgaaatta aaaagtattc 6120 caaaaaaata tttaacagtgaaattggtca agtcattagt gttgctgatg gaattgccaa 6180 ggttagtgga cttgaaaatgctttattaaa tgagttaatt caatttgaaa ataatattca 6240 aggaatagta ttaaaccttgaacaaaatac agtcggaata gcactttttg gtgactattc 6300 ttcgttacga gaaggcagtaccgctaaaag aacccacagt gtaatgaaaa ctcctgttgg 6360 tgatgttatg cttggtagaatcgtcaatgc acttggtgaa gcaattgatg gtagaggtga 6420 tattaaagct actgaatatgatcaaataga aaaaattgct ccaggtgtaa tgaaaaggaa 6480 aagtgttaac caaccacttgaaactggaat cttaacaatt gatgctttat ttcctatagg 6540 taaaggacaa cgtgaattaattgttggtga tagacaaaca ggtaaaactg ctattgcgat 6600 tgacactatc attaatcaaaaagataaaga tgtttattgt gtttatgtag caattggtca 6660 aaaaaattca tcagtagcacaaattgtaca ccaacttgaa gttaatgatt caatgaaata 6720 cactacagtg gtttgtgctacagctagtga ctctgattcc atggtttatt taagtccttt 6780 tacaggaata actattgctgaatattgact taaaaaagga aaggatgttt tgattgtatt 6840 tgatgacctt tctaagcatgctgttgctta cagaactctt tcactcttgt taaaaagacc 6900 acctggtaga gaagcttttccaggagatgt tttttattta cattcaagac ttttggaacg 6960 tgcatgcaag ttaaatgatgaaaatggtgg tggctcaatt acagctttac caattataga 7020 aactcaagct ggtgatatctctgcatatat tcctacaaat gttatttcaa ttactgatgg 7080 ccaactgttt atggttagtagtctatttaa cgctggacaa cgccctgcaa ttcaaattgg 7140 tttatcagtt tcaagggttggtagtgcagc acaaacaaaa gcgattaaac agcaaactgg 7200 cagtttaaaa ctagaacttgctcagtatag tgaacttgat agttttagtc aatttggtag 7260 tgatcttgat gaaaatacaaaaaaggtttt agagcatggt aaaagagtaa tggaaatgat 7320 taaacaacca aatggtaaaccttactctca agtccatgaa gcattatttt tatttgctat 7380 taacaaagct ttcattaagtttattccagt tgatgaaatt gctaaattta aacaaaggat 7440 aacagaagaa tttaatggttcccatcctct gtttaaagag ttatctaaca aaaaagaatt 7500 tactgaggat ttagaaagtaaaactaaaac cgcttttaaa atgcttgtga aacgttttat 7560 cagtacatta acagattatgatattaccaa atttggtagt attgaggaac ttaattaatg 7620 gcttttatac aagaaattaagcgcagaatg aatacagtaa aatccaccat taagataact 7680 aatgcaatga aaatggtgtcacgcgctaag tttattaagt tcaaaaaaca gtttcaagaa 7740 attagtttgt tttttaatgaattttataaa gctgttggcc aagtagttgt ttctttaaaa 7800 gaaccaaaaa agaaaccagataaccaaaaa actttatgga taatgatgag ttcttcttta 7860 ggactttgtg gacagcataattcgaacatg aataagttat taaaagctaa ttttaaagct 7920 gatgataaaa tcttttttttaggtagaaaa aaccaatcat tttgaaataa aaatagtcaa 7980 tataatcctg ctgttggatttattgatatc caagatcgtg atattaattt tgattattgt 8040 caaacgatat ttgatcagattatggatgca tttaaagagt ttaaacttga tcgaatttgt 8100 atggtttaca ctaaatttaaaaactcatta atccaacaat ctcagctctt tcaagttttt 8160 cctttcgatg ttgaaacttttaaaacttta aatccggttg taactgatca acaacttgat 8220 tttgagccag atcaagccacgataattaat ttaattactc cacagttttt tgatgtggct 8280 ctgtatggtg gccttgttgaaactaagtta tgtgaatcag cttctagaca aaatgcaatg 8340 gaagctgcta caaagaatgctaaagattta cttgataaat acactttaca atttaacaag 8400 ctaagacaaa actctattacagaagagatt attgaagtta taggaggtat gaattaaatt 8460 gataaaaaaa gaaaacctaacatatggtaa agttcaccaa gtcattggtc ctgtagttga 8520 tgttatcttt tcagaaagtaaacaattacc tagagtttat gattgtttga gtgtacaact 8580 aaaaaaaagt gagctttttttagaagcaac ccaattaata ggtgatgaca ttgttcgttg 8640 cattgcatta ggtcctacagaaggattagc acgtaatgtt aaagttacta actataacca 8700 tccaatagag gtacctgttggcaaaaatgt attgggaagg atgttcaatg ttttaggtga 8760 acccattgat ggaaaagaaccattaccaaa aaaaccaaag ctatcaatcc atcgtaaccc 8820 acctgctttt gatgaacaaccaaatactgt tgatattttt gaaacaggaa taaaagtaat 8880 tgatctttta actccttacgttaggggggg taaaattggt ttatttggag gagctggtgt 8940 tgggaaaact gttttggtgcaagaattaat tcataacatt gccaaagaac attctggttt 9000 aagtgtattt gctggagttggtgaaagaac aagagaaggt aatgatcttt actatgaaat 9060 gattcaaggt ggggtgattgataaaacagt tttagttttt ggccaaatga atgaaccacc 9120 aggagctaga atgagagttgctttaactgc tttaacaatg gcagaatatt ttcgtgatca 9180 tgataatcag aatgtgctgttattcattga caatattttt cgttttactc aagcaggtag 9240 tgaggtttca gcattacttggtagaatgcc atctgctgtt ggctatcaac caactttagc 9300 tattgaaatg ggtaagttacaagaaagaat tgcttctacc aaaacaggtt ctattacatc 9360 tgttcaagct atctatgttccagcagatga tctaacagac ccagcacctg caacaacatt 9420 tacccatctt gatgctaaaacagtgttgga tcgtaatatt gcagcactag gtatttttcc 9480 agcaattaat cctttagaatcaacaagtcg tttattagat cctagtgttg ttggtatcaa 9540 ccattataaa gtcgctttaggagtgcaaaa tatcttgcag cgttttgcag aattacaaga 9600 tatcattgct atactagggattgatgaatt gtctgatgaa gataagatta ttgttgaaag 9660 agcaagaagg atacgtaactttttatccca accttttttt gttgctgaaa agttttcagg 9720 tattgcaggt aaatatgtatctttaaatga tactgttcaa tcttttaaag aaattttgga 9780 aggtaagcat gatcatttgcctgaacaagc attcttttat gttggaacca ttcaagaggc 9840 tgttgaaaaa gcaaaaagattaaatcaaga gtttgataaa actaaatagt tttatgaagt 9900 tattgcgctt tttggtacttagtcctagtg gcataaaact agataaaacc attattagtg 9960 cgcaagttaa aactactgaaggttacatag gattaaattt taatcgcgct cctttgattg 10020 ctgctattca atcccatctgtgcaaaatta tttttgctga tcaaacaaaa agagaagcaa 10080 ttattggtgc tggtttaatgcttattaaaa aaacagaagc taagattttc acagaaaatt 10140 ttgtttttgc tgatgaagttgatattaatg aaaccttaaa aagaaaaaca gaacttgaaa 10200 gaaaaattca ccatatcaaggatgctaagc taaacgttaa aattgaacaa aatttaatgt 10260 ttgaactatt aaaactttcaagtaagaaaa aataaaatta ttatatgttt taagatttct 10320 attaattcaa gtaatatgaaagaaatttat tttggtggtg gttgtttttg aggaatagaa 10380 aaatattttc aacttattaagggtgttaaa aaaacatctg ttggttatct caactctagg 10440 attagaaatc ctagttatgagcaggtttgt tctggttata ctaatgctgt tgaagctgta 10500 aaagttgaat acgaagaaaaagaaatttct ctttcagaat taattgaagc actttttgaa 10560 gttattgatc caactataagaaatagacaa ggtaatgata ttggaacaca atatcgtact 10620 ggtatttatt gaactgatagcagtgatgaa aaaataatta atgataagtt cttaaaactt 10680 caaaaaaact acagtaaaccaattgttaca gaaaataaaa aagtagaaaa ttattatctt 10740 gctgaagaat accatcaggattatttaaaa aagaatccaa acggttattg ccacatcaaa 10800 tttgactaa 10809 821247 DNA M. genitalium 8 taattaatga ttcattcagt gaggaaaatc aatagtagatatgcttgtta actttaaatt 60 gatgcttcaa aaagcaaagc taggtaaata tgcaatccctcacattaaca tcaataacta 120 tgaatgggcc aaagctgttt taacagcagc aaatcaagctaatagcccaa ttattgtttc 180 agtatctgaa ggtgctttaa agtacatgtc tggttatagtgttgttatcc cgcttgttaa 240 gggtttaatt gaatcactaa gtgttaaagt accagtgacattacatttag atcatggtag 300 ttatgatgca tgtatccaag cattacaggc tggatttagttcagtaatgt ttgatggttc 360 acatttacca tttgaagaaa atttcaataa atctaaaaagttaatagaga tagcacaaaa 420 aacaaatgct tctgttgaac ttgaagttgg tactattggtggagaagaag atggtgttat 480 aggacaaggt gagttagcta atgttgatga atgtaaacaaatcgctagtt taaaaccaga 540 tgctttagca gcaggaattg gtaatatcca tggtatctatcctaagaatt gaaaaggatt 600 aaactttcct ttgattgaaa caatatcaaa aattactaacttacccttag ttttacatgg 660 tggctctgga atcttagaaa atgatgttaa aaaagcaattagtttaggga tttgcaaact 720 aaatattaat actgagtgtc aattagcatt tgcacatgaaattagaaaat acattgaatc 780 aaataaagac ttggatctta acaaaaaagg ttatgatcctagaaaacttt taaaagaacc 840 tactcaagca attgttgata cttgcttgga aaagattgatttgtgtggtt ctagaaataa 900 agcatagttt aatacctggt ggtaagggga ttaatgttgctattgtaatg aaatcacttg 960 gttttgatcc aactgtcatt acttttttgg gacaacccactaaaaactta tttttagagt 1020 tggtaaaacc ttatgatcta aatatagtta gcttcatttctgaaactaaa acaagaatta 1080 accttaagtt attaaaagat gaaaaaacta ctgaaattaatgatttaagt cctttaataa 1140 cagatgctaa tctaactgaa ttgttaactt ttttaaaagctaatgttaag aataatgatt 1200 tggttatcat caacggaaga tttaaatttg aagctttagaaaaagttcta aacttggtct 1260 ttacattaac agaaaatgtg gttatagatg ttgatgaaagcaaaatgtta acgcttttaa 1320 atcagtctaa accactagtt atgaaaccta acattgatgagtttcaaact atgattaata 1380 ctttttttca cgatcaacaa agcttaatag cagcaattaaaaaatttcat tactgtaagc 1440 tcttattatt atctgatggt gacaaaggag cttatctttttgatcagaat aagttattgt 1500 ttgtaagttc tatcactcct aaacaagtag ttagcaccacaggagcaggt gatactttgt 1560 tggcagtttt tttagcaaat ttgattctaa aggtagatttaaaaactgct ttgattaaag 1620 caactaacta tgcaagtgca acaattagta agttaggtgttgttgatagt aaagacaaaa 1680 ttagtgttat aaccccaaaa agttactatt tataaaaatcctaaacaggt tgaagagatc 1740 cattgaattt agattatgaa atacttatat gccactcaacaccttacttt aaatgctatt 1800 aagcatgcta agggaggaca tgttggcatg gccattggtgcaagtcctat cttatttagt 1860 ttatttacta aacactttca ctttgatcct gaccaaccaaagtggatcaa cagagatcgc 1920 tttgttttaa gtgctggcca tggtagcatg gcattatattcaattttcca ttttgccgga 1980 cttatttcta aacaagagat cttacagcat aaacatggtcaaattaacac ttcttcccat 2040 cctgaatatg ctccaaataa cttcatagat gcatcaacaggccctttagg tcaaggcttt 2100 ggcatggcag ttggcatggt gttagcacaa aagttattagctaatgaatt taaagagcta 2160 agtgataaat tgtttgacca ttacacctat gtggttgttggggatggaga tctacaggag 2220 ggggttagtt atgaagttag tcaaattgct gggttatataaattaaataa actaattgtg 2280 cttcatgatt caaatagagt gcaaatggat agtgaagtaaaaaaagttgc taatgaaaat 2340 ctaaaggtta ggtttgaaaa cgttggttgg aattacatccatactgatga tcaactagaa 2400 aatattgatc aagctattat taaagccaaa caatcagataagccaacttt tattgaagtg 2460 agaacaacta ttgctaaaaa cacccacctt gaagatcagtatggaggaca ttggtttatt 2520 cccaatgaag tggactttca actttttgag aaaagaacaaatactaactt taactttttt 2580 aattatccag atagtattta ccactgattc aaacaaactgttattgaaag acaaaaacaa 2640 attaaagaag attacaacaa tttgctaatt tctcttaaagacaaaccact ttttaaaaaa 2700 tttactaatt ggattgacag tgattttcaa gccctttatcttaaccaact agatgaaaag 2760 aaagtagcaa aaaaagatag tgctactaga aactatttaaaagatttttt aaaccaaatt 2820 aataatccta attccaactt gtattgctta aatgctgatgtatcacgttc ttgttttatc 2880 aagataggtg atgataatct ccatgaaaat ccttgttctagaaatatcca aataggaatt 2940 agggagtttg caatggcaac aataatgaat ggtatggcacttcatggtgg tattaaagtg 3000 atgggtggta cttttttagc atttgctgat tattcaaagccagcaattcg cttaggtgca 3060 ttaatgaact taccagtatt ttatgtttat acccatgactcttatcaagt agggggtgat 3120 ggtcctactc atcaacccta tgatcaacta ccaatgttaagagcaattga aaatgtttgt 3180 gtatttcgtc cttgtgatga aaaggaaact tgtgctggatttaactatgg tcttttaagt 3240 caagatcaga caactgtttt ggttttaaca cgtcaacccttaaaatccat tgataacact 3300 gatagtttaa aaacactgaa gggtggttat atccttttggatagaaaaca acctgattta 3360 attattgctg ctagtggtag tgaagtgcaa cttgcaatagagtttgaaaa agttttaact 3420 aaacaaaatg taaaggtaag aattctgtca gttcccaatataactttact tttaaaacaa 3480 gatgaaaaat atctaaagag tttatttgat gctaacagttcacttatcac catagaagct 3540 agtagtagct atgagtggtt ttgctttaag aagtatgttaaaaaccatgc tcatttagga 3600 gcttttagtt ttggtgaatc tgatgatgga gataaagtttatcagcaaaa agggtttaat 3660 ctggaaaggt taatgaaaat atttacttcc ctaagaaattaattcctaag ctgtttggtt 3720 aataaaattt agtagtttta aaatgcagat tagtttagttaaaatccgca ataagtttaa 3780 acaaagaaac cgtggttctt ttcgtcagtg agttggtaagctttccaacg gtttgatgat 3840 ccctattgca gttttgcctt tagcaggtat ttttttaggaatcggtgatg ccatttcttc 3900 caattcatct ggcattgttg gtgtgaaatt ttttggtgaatttattaaac aaggtggtaa 3960 tgtagttttt gctaacttac ctattttgtt tgcagttgcaattgcgatca ccttttctca 4020 agatgcaggg gttgctggat tttctgcttt tgttttttgggccacaatga acgcgtttat 4080 gagttcatta attattcctg ttgatgcaaa taatactgcttcaggttata acatccttta 4140 ttgaaaagca gtacctcagt cagcaattgc ttctactttaggattaaatt cactttcaac 4200 ttcagttttt ggtgggatta tagtaggggc tttaactgcatatttatata acaagtttta 4260 tgcaattaga ttgcctgatg taattgggtt ttttagtggtactaggtttg ttcctattat 4320 ttgtatgact attgctattc cagtagcatt acttttattgatggtttgac ctggtgtttc 4380 tatcttatta aatttaatag gaactgggct tggaatcttaggtggaagag gatatggtgc 4440 taacagttta atctttggat atatagaaag agcactaattccttttggag tacatcatgc 4500 cttttatgca ccattatgat atacaagtgc aggcggtagtttgcaagaaa ttgcaaatca 4560 acaagtttgg attagagctc ctggtagtga ttatgtaaccagagtgatag gttgagaaga 4620 ttttaatact ccaggaaaat gagttattcc tgctgctttagctaatggaa caagtggaat 4680 gatgaatgga gctactacaa caggacaaga tagtacatctgcactttcaa aatacatgag 4740 taaagaatca acaaactttc taagttgaaa agaacttgttgatggtctta cacgtaaagg 4800 taactttgat gaattggcta aaaacggttt attagatggttctaacaaga tttgaattgg 4860 tttaaaccag tcagggatct taggtaaaaa agtactgttaagtgatggta aggactacac 4920 tattaccttt aaaacttttg ctaacaccac gccaacattctgaagccatg gtgctcatgc 4980 acttttacca attagtggaa ctccaagtgc aataactaatggagttactg ttaatggtac 5040 tgctaattct aaaacctata atgtcagtca gttcactgttgcagttcctt ctttaaaccc 5100 agcacaatat tcccaaggta aattcccatt catgctaattggaattccag cagctggact 5160 tgcaatgatc ttagctgctc ctaagggtag aagaaaagaagctagttcta ttattggtag 5220 tgctgcattc actagttttc taacagggat caccgaaccttttgaattta cctttctttt 5280 cttagcacca tggttattct atggtatcca cgctgtattagctgcagtaa gcttttgatt 5340 aatgaactta ttgagtgcta acgttggaca aaccttctcaggttctttca ttgactttat 5400 cttgtatggg gctttacctg atggtagggg ttgattagcaaactcttact tagtacctat 5460 tattggtatc tttttagcat tgatttattt ccctaccttctatttcttga caattcgctt 5520 taacttagca actcctggta gaggtggtaa gttaattactaaaaaggaat atttagcagc 5580 aaaagcagct caaaaaactg atcaaactac taacactaactttaatcaaa cccaaattga 5640 agctggtatg ttactaagag cttatggtgg aagtgaaaacattgctgaat taggggcttg 5700 cattactaaa ttaagagtaa cagttaaaaa ccctgaacttgttaatgaaa ctattattaa 5760 agacttggga gcagctgggg taatgcgtac cactccaacattctttgtag cagtgtttgg 5820 tactcgagct gctgtttata aatcagcaat gcaagatattatccaaggca aagtaaattg 5880 aacagagttg caaaaagtct tagataaaaa tgatagtactgttgaaaaac cagaaataaa 5940 accaacccca gttttaaaag ttcaagatga aattgtgatcctctcaccag ttaatggcac 6000 cttaaaaccg ctcacccaag ttcctgatga taccttcaaaaatcgtttgg taggagatgg 6060 aattgctatc ttacctagcg atgggcactt caaagcaccaggtgatgtgg gtgtgaaaac 6120 tgaacttgct ttccctactg gtcatgcctt tatctttgatgttgatggtg tgaaagtaat 6180 gcttcacatt gggattgata cagtaaaaat taatgctgataaaaaaccag gggaacaact 6240 tgaagtgttt gatgtaaaaa caaaacaagg agaatacactaaattaaaga gtgaaagtgt 6300 tgttgaagtt gatttaaaga aacttaaacg aaagtatgatccaatcactc ctttcattgt 6360 gatgcaagaa tcacttgata acttcaagtt ggtgccaattcgccaacgtg gtgaaattaa 6420 agttggccaa cctttattta aactaattta taaagataagaagagttaaa gaagtataga 6480 aaaatgatta attaaaatca actgcaaaag tgtttatgagtgataaatta ttaacaattg 6540 acttaagtca tgtttatgga tttgataaag aaattatttttaagaaatac caaaaaaaag 6600 tagatcaaat tcaccaagat tttctagctc ataaacttgctgatggtcac atgactgggt 6660 ggtatgacca acctgatcaa aaccaccaat tccttttaaaaaccattaat caaattgaca 6720 aaaagtttaa aagtttaaaa gtaactgaca ttgtttatgttggtattggt ggttctttta 6780 ctggtattaa aacagtttta gatttcttaa aaccaaaacaaagaacagga ttaaaaatcc 6840 actttgtccc tgacctttct gcttttcaag ctgcaagtgttattaaggaa attaaaaata 6900 aatcatgggc tctaattacc acttctaagt ctggtagaaccctagaacca gcactgaatt 6960 tccgcatttt tagaaactta ttaaacaagc gttatggcaacaaacactac caaagagtag 7020 ttgttattac tgatgaaaaa aagggattac taaccaaaatggcatcaaat catggttacc 7080 aaaagttagt tattgattca aatatcggtg ggcgtttttcaactctatct cctgctggtt 7140 tgttactagc caaacttttt ggtcatgatc ctaaggccatcttaaaagga acattacaag 7200 ccaaaaagga tttgcaaaca acttcacttg aaaacaattctgcatacctt tatgcagtag 7260 ttagacattg actatacacc acaaaaaaat tcaaaattgaagtttgcatt gcttatcaca 7320 gtttgtatga atatttgtta ttacagcatc gacaactttttggtgaatca gaaggtaaga 7380 acgataaatc tttatttcct actttttcga tttttactgttgacttacac tcaatgggac 7440 aactctatca agaaggggaa aaagtgtttt ttgaaacagtaattgatgtt aaaaatccac 7500 ttgttaatat taatttacct ccatctgatt ttgacaatgatgatgaactt gatttcttgt 7560 tagataaaag cttaaatgag atttcagatg ttgcaattgattcagttatt aaagcgcact 7620 accaagcaaa tgtaagcatt attaaattaa ctttaaaagaacaatctgca tttatgtttg 7680 gttattttta cttttgactc tctgttgcta cagtgatgagtggatcatta ttagggcata 7740 atgtctttaa tcaacctggc gttgaagttt ataaaaagttaatgtttgaa aaactaagaa 7800 gtggccacta acaaccgcta tggtgatgaa taaccttatataatttacaa catggataaa 7860 atagctattt taacttcggg tggtgatgct agtgggatgaatgccaccat cgcttatcta 7920 accaaatatg caattgcaaa gcaattggaa gttttttatgtaaaaaacgg ttattatggc 7980 ttgtatcaca accattttat caccagtaag gaacttgatttaactgactt tttctttatg 8040 gggggaacag taataggatc aagtcgtttc aaacagtttcaagatcctag cttacgaaaa 8100 caagcagttt taaacctcaa aaaacgtggt attaacaaccttgttgttat tggtggggat 8160 gggagttata tgggtgctaa agcactcagt gaattaggattaaactgctt ttgtttacct 8220 ggtacgatcg acaatgatgt caattccagt gaatttaccattggtttttg aactgcttta 8280 gaagcaattc gggttaatgt tgaagcaatt tatcacaccaccaaatccca taaccgctta 8340 gcaatcatag aagtgatggg gcgtgattgt agtgatctgaccatctttgg ggggttagct 8400 actaatgcta gttttgttgt tactagcaaa aatagcttggatctcaatgg ctttgaaaaa 8460 gcagtgagaa aggtgttgca attccagaac tattgtgttgttttggttag tgaaaacatc 8520 tatggtaaga acggtttacc tagtttagaa atggttaaagagcactttga aaacaacgca 8580 attaagtgta acctagtttc actaggacac acccaaaggggctttagtcc taatagtatc 8640 gaactctttc agattagttt aatggctaaa cacacgattgatctggttgt aaataatgcc 8700 aacagtcaag taatagggat gaaaaacaac caagcagttaactatgattt taacactgct 8760 tttaatttac caaaagctga tagaaccaag ttacttaaccaagttaacac tgcaattatt 8820 taacgatgat tgaccattta aaaagaacaa agataatcgctacctgtggc ccagctttaa 8880 caaaaagctt ggttagctta aagatgcttg atgataatgagtatgcagct attaaaaagg 8940 ttgcttatgc caacattgaa gcaattatta aaagtggggttagtgtgatt aggcttaact 9000 tctctcatgg tacccatgaa gaacaacaag tgaggatcaagatagtaagg gatgtagcga 9060 aagcaatgaa catccctgtt tctattatgt tagatacaaatggtcctgag atcaggatag 9120 tagaaactaa aaaagagggt ttgaaaatca ccaaagatagtgaagtgatt atcaacacca 9180 tgagtaaaat gatcgctagt gacaaccagt ttgctgtcagtgatgctagt ggcaaataca 9240 acatggttaa tgatgtgaat ataggtcaga aaatccttgttgatgatggt aagttaaccc 9300 tggttgtcac aagggttgac aaacaacata accaggttatctgtgttgca aaaaacgacc 9360 acacagtttt cactaaaaaa agacttaacc tacccaacgcacagtactct atcccttttc 9420 tcagtgaaaa ggatctgaag gatattgact ttggtttaagccaaggtatt gactatattg 9480 ctgcctcttt tgttaatact gttgcagata ttaaacaactgagagattat ctgaaattaa 9540 agaatgctag tggggtgaag atcatcgcta agattgaatctaatcatgct ttaaataaca 9600 ttgataagat cattaaagct agcgatggga ttatggttgctaggggtgat ttgggccttg 9660 aaatccctta ttaccaagtc ccttactgac aaaggtacatgattaaagct tgtcgctttt 9720 ttaacaagcg ttctattact gcaacccaaa tgcttgattcactagaaaaa aacatccaac 9780 caacccgagc tgaagtgact gatgtttact ttgcagttgatcggggtaat gatgcaacta 9840 tgttaagtgg ggaaactgct agtgggcttt accctttaaatgcagtagcg gtgatgcaaa 9900 agattgataa acaatcagaa accttctttg attaccagtataacgttaac tattatttga 9960 aaaactccac ggcaaataaa agtaggtttt gacacaacgttgttttacct ttaacaaaaa 10020 agactgttcc taaaagaaaa cttgttaaca gtgcctttaagtatgacttt attgtctatc 10080 ctactaataa cattaacagg atctatgcat tatcaaacgcacgcttagca gcagcagtta 10140 ttattttaac caacaacaaa cgggtttaca ctggccatggtgttgattat gggatcttct 10200 gttatttaat tgataaaaac cccaaccagc taaccaaagctgaactgatt gaacttgctt 10260 gaaaagcaat taaccactat caggcttatg gtgatttagaaaaactcaaa cagtgtttag 10320 ctgtctataa tgaaacaatt atcaatcttt agtcctaaaaaatagcttag ttttaaatta 10380 gcatagaaat atatggcaat cttgattaaa aataaagttccaactaccct ttatcaggtt 10440 tatgataatg agggtaaatt aattgatcct aaccacaaaattaccctaac tgatgaacag 10500 ttaaaacacg cttattactt aatgaacttg agtagaatgatggacaaaaa gatgttagtt 10560 tgacagcgtg ctggtaagat gttaaacttc gctcctaatttgggagagga agctttacag 10620 gttggaatgg gattaggttt aaatgaaaat gattgggtttgtcctacgtt tcgtagtggg 10680 gctttaatgt tgtatcgtgg ggtaaaacca gaacaacttttactctactg aaatggtaat 10740 gaaaaaggta gtcagataga tgctaaatac aaaactttacctattaacat caccattggt 10800 gctcagtatt cccatgctgc tggattaggt tacatgttgcactataaaaa gcaacctaat 10860 gttgctgtta ctatgattgg tgatggaggt acagctgaaggggaatttta tgaagcgatg 10920 aacattgcaa gcatccacaa gtgaaacact gttttttgtattaacaacaa tcagtttgct 10980 atctcaacaa gaactaaact tgaatctgct gttagtgatctaagcgttaa agcaatagca 11040 tgtgggatcc caagggtaag ggttgatggt aatgatctaattgctagtta tgaagcgatg 11100 caagatgctg ctaattacgc tagaggtggt aatggaccagtcttaattga gttcttcagc 11160 taccggcaag gtcctcacac cacttcagat gacccttctatctacagaac caaacaagaa 11220 gaggaggagg gaatgaagag tgatccagtg aagcggttgcgaaacttctt gtttgataga 11280 tcaattctta accaagctca agaagaagag atgttcagcaaaattgaaca ggaaatccaa 11340 gctgcttatg aaaagatggt actagatact cctgtatcagtagatgaggt gtttgattac 11400 aactatcaag aattaacccc tgaactagtt gaacagaaacagattgcaaa aaaatacttt 11460 aaagactaat ttaaaaaaag ataactatgt caaaaatccaagtaaataac attgaagcgt 11520 taaacaacgc aatggatctt gcactggaaa gagatcaaaacgttgtactc tatggccagg 11580 acgctggttt tgaagggggt gtgttccgtg caactaaaggcttacaacaa aagtatggga 11640 gtgaaagggt atgggattgt cctatagcag aaaactctatggctggtatt ggggttgggg 11700 ctgctatagg tggtcttaaa cctattgtag agatccagttttcaggcttt tcattcccag 11760 ctatgtttca aatctttgtc catgctgcta ggattagaaaccgttctcgt ggtgtatata 11820 ccgctccact agtagtgagg atgccaatgg gtggggggattaaagcattg gaacaccaca 11880 gtgaaacatt ggaagcaatt tatgcacaga ttgctgggcttaaaacagtg atgccatcaa 11940 atccttatga taccaaagga ctttttctag ctgctattgaatcacctgat cctgttatct 12000 tttttgaacc aaagaagctt tatcgtgctt ttcgtcaggagattcctagt gattattaca 12060 ctgtccctat tggtgaagcc aacttgatta gtgaaggtagtgaacttaca atagttagct 12120 atggtcctac aatgtttgat ttaattaact tagtttacagcggggaattg aaagataagg 12180 gaattgagtt aattgacttg cgtactatct ccccttgagataaacaaaca gtatttaact 12240 cagtgaagaa aacaggaaga ctacttgtag tgactgaagcggtgaaaagt ttcactacaa 12300 gtgcagagat tatcacttca gtaactgaag aactattcacttatctcaaa aaagccccac 12360 aacgggtaac tgggtttgat attgttgtgc ctttagctagaggtgaaaaa taccagtttg 12420 aaattaatgc acgggttatt gatgcagtta atcaacttttaaaataacac ttttttaaaa 12480 tatagttacc tagctttatt ttttagagct aggtacctcatttcataaat taaagtgatg 12540 gaagacaaca agaaatgctg ccaatgcaag tgcgaatgcgctaagtgcaa cagctgctgt 12600 aaaaagtaag acaaaatttt tgtctaacaa ctaaaaagccagtaactaaa ctggcttttt 12660 ttatttgtta tagatcacta ctattaaatt taaactttaagtactatcaa tacgatatgg 12720 caaatgagtt taaattcact gatgttggtg agggtttacatgaaggaaaa gtaactgaaa 12780 tcttaaaaca agttggtgat cagatcaaga tagatgaagctttatttgtt gttgaaactg 12840 ataaagttac aactgaacta ccttctcctt ttgcaggtacaattagtgct attaatgtta 12900 aagttggtga tgttgttagc attggtcagg tgatggcagttattggtgaa aagactagta 12960 caccacttgt tgaaccaaaa cctcaaccaa ctgaagaagtagctaaggta aaagaagcgg 13020 gggcttcagt agtaggggaa attaaggttt ctgataacctctttcctatc tttggagtaa 13080 aacctcatgc aactccagct gttaaagaca ctaaagttgcaagtagtact aacattactg 13140 tagaaacaac ccaaaaacca gaaagtaaaa ctgaacagaaaaccattgct atctcaacaa 13200 tgcgtaaagc gattgcagaa gcaatgacaa agtcgcacgcaattatccca accactgtat 13260 taacttttta tgttaatgca accaagttaa aacaatatcgtgaaagtgtt aatggttatg 13320 ctttaagtaa gtattccatg aaaatttctt actttgctttctttgttaaa gcaattgtta 13380 atgcgcttaa gaagttccct gtttttaacg ctagttatgatcctgatcaa aacgaaattg 13440 ttttaaatga tgacattaat gtaggaattg ctgttgatactgaagaaggt ttaattgtcc 13500 ctaacattaa gcaagcccaa accaaatctg tggttgaaattgcccaagca attgttgatt 13560 tagctaacaa agctagaaca aaaaagatta agttgactgatttgaataaa ggtactattt 13620 cagttactaa cttcggttca ttaggagcag ctgtaggtacacctattatt aagtaccctg 13680 agatgtgtat tgttgctact ggtaatttag aagaacgcattgttaaagtg gaaaatggaa 13740 ttgcagttca taccatctta cctttaacaa tagctgcagaccaccgctgg gttgatgggg 13800 cggatgttgg taggtttggt aaggagattg caaaacaaattgaggaatta attgatctta 13860 cagtagctta atttatggat tatgatctaa ttattttgggtgctggccct gctggttata 13920 ttgctgcgga gtatgctggc aaacataaac ttaaaaccctagtgattgaa aagcaatact 13980 ttggtggggt gtgtttaaat gttgggtgta tcccaactaaaacgttgtta aaaagagcaa 14040 agattattga ttatttagtt catgccaaag attatggtatcactattaat ggtcaagcta 14100 aacttgattg aaaacaactg ttaaaacaaa aacaggaagtagttgataaa ttagttgcag 14160 gggtaaaaac aattattaag ggtgctaagg tagaaagtattgaaggtgaa gctactgtta 14220 tagataaaaa caaggtgcaa gtaaacaaca caacttacaccactaacaac attattgttg 14280 caaccggatc aagaccaaga tacttaactt taccagggtttgaaaaagca caacaagctg 14340 ggtttatcat tgactcaacc caagctttgg ctttagagggagtacctaag aagtttgttg 14400 tagttggggg aggtgtgatt ggggttgagt ttgcttttttatttgcttca ttagggagtg 14460 aagtgaccat tatccaaggt gttgatagga ttttggaggtttgtgatagt gatgtttctg 14520 aactgataag taaaacctta aaaaacaaag gagttcagattattaccaat gctcatgttg 14580 ttagagctga aaacaaccaa ctgttttaca cagttaatggagttgaacag tctgtaattg 14640 gtgataaaat cttagtttct ataggaagaa ttgctaacacagagtgttta gatcaacttg 14700 atttaaaacg tgaccataac aacaaaattg ttttaaatgaaaaactacaa acatcaacta 14760 caaacatcta tctaataggt gatgttaaca cgcaaatgatgttggcacac tacgcttacc 14820 aacagggcag atatgctgtt gatcaaattt tgaaccaaaaccaggtaaag cctgctgaaa 14880 aaaacaagtg tcctgcttgt atttacacaa atcctgaagttgcttttgta ggttatagtg 14940 agatggaatt gcaaaaagaa aagattgatt atgtcaaatcttccttgcca tttatttata 15000 gtggtaaagc aattgcagat catgaaacca atgggtttgtcaagatgatg tttaatccta 15060 aaactggtgc tatcttaggt ggatgtatta ttgctagcactgctagtgat attatcgctg 15120 agcttgcttt ggtgatggaa aacaacctca ctgtgtttgatattgccaat tctatctcac 15180 cccatcctac catgaatgaa atggtaactg atgtttgtaaaaaagcgatc tttgattact 15240 ttagttaaaa taggctaaag tattaaaatc taattattaaattaaagtat ggcagcaaag 15300 aatagaacca ttaaggttgc aatcaatggt tttggaagaattggaagact tgtttttcgt 15360 tctcttctca gtaaggcaaa tgttgaagtt gtagcaattaatgatttgac ccaacctgaa 15420 gttttagcgc acctgttgaa atatgattca gctcatggtgaattgaaaag aaagattact 15480 gttaaacaaa acatcttgca aattgataga aaaaaggtttatgtttttag tgaaaaagat 15540 ccccaaaatt taccttggga tgaacatgat attgatgtagtaattgaatc aactggtagg 15600 tttgtaagtg aagagggtgc ttctctccat ttaaaagcaggtgctaaaag agtaattatt 15660 tccgcacccg ctaaagaaaa aactatcagg acagttgtttacaatgttaa tcacaaaacc 15720 attagtagcg atgataagat catctcagca gctagctgtactactaactg tttagcacca 15780 ttagttcatg tacttgaaaa gaactttggg attgtttatggaacgatgct aacagttcat 15840 gcatatactg cagatcaacg cttacaagat gctcctcataatgacttacg tcgtgctcgt 15900 gctgcagctg ttaacattgt gccaacaaca acaggagcagctaaagcaat tgggcttgtt 15960 gttccagaag caaatggcaa acttaatggg atgtcactccgtgttccagt gttaactggt 16020 tctattgtag agttaagtgt tgtacttgaa aaaagtccatctgttgaaca agtaaatcaa 16080 gccatgaagc gatttgcttc cgcttctttt aaatattgtgaagatcctat tgtatctagc 16140 gatgtggtaa gttctgaata tggttcaatt ttcgattctaaactaaccaa tattgttgaa 16200 gttgatggca tgaaacttta taaggtgtat gcatggtatgataatgaatc ttcctatgta 16260 caccaactag tgagagtagt tagctattgt gctaagctctaatatgctta atttcaaaac 16320 actccaagca attgattttc aaaacaaaac cgttgttttaagaagtgatt ttaatgtccc 16380 aatgatcaat ggggttatta gtgatagtga aagaattttagctggtttgg atactattaa 16440 gttcttagtt aaaaagaact gcaagatagt gctactatcacacctttcaa ggattaagag 16500 tttagaagat aaactaaaca acaaaaaatc tttaaagccggttgctgaat tactccaaca 16560 actcttacca actgtaaagg ttcaattttc ttgtaaaaacactggtgctg aagttaaaca 16620 aaaagtgcaa gcattagcat tcggtgaaat ccttctccttgaaaacactc gctattgtga 16680 tgtaaacgat aaaggagaaa ttgttaaatt agaaagtaaaaatgatcctg aactagcgaa 16740 attctgggct agtttagggg aaatttttgt taatgatgcatttggtactg cccatagaaa 16800 acatgcttct aatgcaggaa ttgcaaagta tgttgcaaaatcctgtattg ggtttttaat 16860 ggaaaaagaa ctaaagaacc tctcttacct aattcaaagcccacaaaaac cctttgttgt 16920 tgttttgggt ggtgcgaaag tatcagataa actaaaggtagttgaaaact tactaaaact 16980 tgctgataat atcttaattg gcggagggat ggtaaatacctttcttaaag caaaaggcaa 17040 agctactgct aattccctag ttgaaaaaga gttaattgatgttgctaagc aaatcttgga 17100 taaagatact cataataaga ttgtgctggc aattgatcaggtaatgggtt ctgaatttaa 17160 agatcaaact ggcattactt tagatgttag tgacaaaattcaagaacaat atcaatccta 17220 tatgtctcta gatgttggat ctaaaacaat tgctttatttgaaagttatt taaaaacagc 17280 caaaactatc ttttgaaacg gtccccttgg agtttttgaatttactaact ttgctaaagg 17340 aacttcaaaa atcggtgaga ttattgctaa aaataaaactgcttttagcg ttattggtgg 17400 tggggattca gctgcagcag ttaagcaaat gcaactatctgatcagttta gttttatctc 17460 cactggtggt ggtgcttctt tagcactaat tggtggggaagagttagtag gtattagcga 17520 tattcaaaaa aattcttaaa acatataata attttattaacaatattttt ctatttaata 17580 tgggaagttc aaatctaaac atcaattcaa aaataaccgatatttttgct tatcaagttt 17640 ttgattctcg gggtgttcca acagtagctt gtgttgttaaattggcatct ggtcatgtag 17700 gtgaagcgat ggttccatca ggtgcttcta caggtgagaaagaagcaatt gaattacgtg 17760 ataatgatcc aaaaaattat tttggtaaag gcgttaacgaagccgttgat aacgttaata 17820 aagttattgc ccctaagctt attggcttaa atgcatttgatcaattaaca gtggatcaag 17880 caatgattaa actagacaat actcccaaca aagcaaaattaggagcaaat gctatattat 17940 ctgtttcact tgcagtatca aaagcagcag caaaagcacaaaacagctca ttatttcaat 18000 acatttcaaa taaattaatt ggattaaata caacaaattttgttttacct gtgccaatgt 18060 taaatgtaat taatggtggt gctcatgctg ataactatattgattttcaa gagttcatga 18120 tcatgccttt aggtgctaaa aagatgcatg aagctttaaaaatggctagt gaaacttttc 18180 atgctttaca aaatctttta aaaaagcgtg gattaaacacaaataaagga gatgaaggtg 18240 gatttgcgcc taacttaaaa cttgcagaag atgcacttgacatcatggtt gaagccatta 18300 aattagctgg atataagcct tgagatgata ttgctattgccattgatgtt gctgctagtg 18360 agttttatga cgaagataaa aaactttatg ttttcaagaaaggaataaaa gctaatatcc 18420 ttaatgcaaa ggattggagt ttaacaagca aagaaatgattgcttactta gaaaaattaa 18480 caaaaaaata tccaattatt tcaatagaag atggtttgagtgaaaatgat tgagaaggga 18540 tgaaccaatt aactaaaacc ataggtagcc atattcaaattgttggtgat gacacttact 18600 gtactaatgc agaacttgct aaaaaaggtg ttgcacaaaatacaacaaac tcgatattga 18660 ttaaattaaa tcaaattggt tctattagtg aaacgattcaaacaattgaa gttgcaaaaa 18720 aagctaactg gagtcaagta atttcacatc gcagtggtgaaacagaagat acaactattg 18780 ctgatttggc agttgctgcc caaactggtc aaattaaaaccggttcaatg tcacgctcag 18840 aaagaatagc taaatacaat cgtttgttgt acatagaaattgaacttggt gataaaggaa 18900 aatacttagg ttgaaatacc tttacaaaca ttaaacctaaaaactttaac atctaagaaa 18960 agaaaatggt ttttgaaaac ttataaaatc tttcatatgcgcacaaggta tttaattggc 19020 aattggaaaa caaataaaaa tttaaaagac gcagttagttttgttgaaca atttcaacaa 19080 aataaactta attacaatgc caaaattggg atagcacctgtttatgttca tctcactgaa 19140 ataaaaaaaa taattagtga tagtctcctt ttatttgcccaagacgctaa ctttattgaa 19200 agtggttcat atactggaac tgtaagcttt actcaacttcaagacattgg tgttaacaac 19260 agtattattg gtcattctga aagaagaaaa tactataacgaaaccagtgc agttattaat 19320 caaaagctct ttgcttgtct aaaagcatcc atgcaagtagttttatgtat tggtgaggct 19380 ttaggacaag agattagctt tcttaaaact gatcttactaattgcttaga tacgattgac 19440 aaaagcttaa ttaaaaattt agttattgct tatgaacctttgtgagcaat tgggacaggt 19500 aaaacagcaa ctcctgaagt tgcaaatcaa accattaaaaccattaggga atatattaat 19560 gacttatatg atgaaaatgt tgctaacaat atctcaattctatatggcgg atcagttgat 19620 cataataata tccaaaaact agcaataatg gaacaaattgatggattttt agttggtaaa 19680 gcatctttag aaattaaaaa ctttttagaa atggctagggtatatgcata aaaaagtttt 19740 attagcaatc cttgatggtt atgggatctc aaatgctatttatggtaatg cagtacaaaa 19800 tgcaaatacc ccaatgctag atgaattaat caattcatatccttgtgtac ttttagatgc 19860 atctggggaa gcagttggat tgcctatggg tcaaataggtaactctgagg taggtcatct 19920 aaatattggg gcaggtcgag ttgtttatac tggactttctttgattaatc aacatattaa 19980 ggatcgtagt ttttttgcaa ataaagcttt tttaaaaaccatagaacatg tagaaaaaaa 20040 ccattcaaaa atccatttaa ttgggttatt ttccaatggaggagtgcata gtcataatga 20100 acatctatta gcactcattg aattgttttc aaaacatgcaaaggtagtat tacatttatt 20160 tggtgatggt agagatgtag caccttgtag cttaaaacaagatcttgaga aattaatgat 20220 atttctaaaa aactatccta atgttgttat tggaactattgggggaagat actatggaat 20280 ggatcgtgat caacgctggg atcgtgaaat gattgcttataaagctttat taggagtttc 20340 aaaaaataaa ttcaatgacc caattggtta tattgaaacgcaatatcaga accaaattac 20400 tgatgaattt atttatcctg caattaatgc caatttaaattctgatcagt ttgcattaaa 20460 caataatgat ggagttattt cctttaattt tagacctgatagagcaagac aaatgtccca 20520 tttgatcttt aacagcaatt attacaacta tcaacctgaattgaaacgaa aagaaaattt 20580 attttttgta acaatgatga attatgaggg aattgtacctagcgaatttg cttttccacc 20640 tcaaaccatt aaaaatagtc ttggtgaagt aattgctaataataatttga agcaattgag 20700 gattgcagaa actgaaaagt atgctcacgt tactttcttttttgatggtg gttttgaagt 20760 taatctcagc aatgaaacaa agacattaat tccttctttaaaagttgcta catatgattt 20820 agctcccgaa atgtcatgta aagctattac tgatgcactactagaaaagc ttaataactt 20880 tgattttact gttttaaatt ttgctaatcc tgatatggtaggtcatactg gtaactatca 20940 agcttgcatt aaagctcttg aagcactcga tgttcaaattaaacgaatag ttgatttttg 21000 taaagctaat caaataacta tgtttttaac tgcagatcatgggaatgcag aagtgatgat 21060 tgataataat aacaatccag ttactaaaca cactattaatcctgtaccat ttgtatgtac 21120 tgacaaaaat gttaacttta atcaaactgg aattttagctaatattgctc ctactatctt 21180 ggaatatctt aaccttagca aaccaaaaga gatgactgcaaaatccttat taaaaaataa 21240 caattaa 21247 9 3075 DNA M. genitalium 9tttattagca cttgaaatga ctcaaaaact aatctaatct atgaaattag aatacaaccg 60gattattgat agcaccttag tcaaagctga tacgcttccc catgaaatag atactttatg 120tgctgatgct cataaatacc agttttttgc agtgtgtgtt aatcctagtt atgttagtta 180tgctaaaaac atcttgaaaa atactgcagt tcaactctgt tgtgttgttg gtttcccctt 240aggacaaaca acccaaaaac agaaggtata tgaagctaag attgctatta aagagggagc 300ggatgaaatt gatatggtaa tgaatattgc tgagtttaaa aaacgttgtg cttgtgttat 360tactgaaatt agagctgtta aaaaagtgtg tggcaagcgt aaattaaaag taattattga 420aactgcactt ttaacaaatg atgaaatcaa agatgcagtt aatgtttgca ttgatggcaa 480tgcagattat gttaaaactt ccactggttt ttctttccgt ggtgcatctt tagaagatgt 540tcagattatg aataatgctg cagcaaattt aattaaaatc aaagcttcag gtgggattaa 600aacagcaaag caatttatag atttatttca agctggagct agtagaattg gaacttcaaa 660tgcggtccaa ataatgcaag aattaaaaaa aatgaaccat gaatatcatt aactgctcaa 720aaaacaataa ttattaataa ataaaaattc ctatggataa acttagatta gaagttgaaa 780gatggttaaa tcatcctaat gttaattggg agttaaaaca acaaattaag gagttgaatg 840aatcagaaat tcaagaactt tttagtttgg aaaaaccttt atttggcact gcaggtgtaa 900gaaacaaaat ggcaccaggt tatcatggta tgaatgtttt ttcttatgcc tatttgaccc 960aaggttatgt taagtacatt gaatccatca atgaaccaaa gcgtcaacta cggtttttag 1020tagcacgtga tacaagaaaa aatggtggtt tatttttaga aacggtttgt gatgtaatta 1080catctatggg tcatttggct tatgtgtttg atgataacca gccagtttca acacctctag 1140tgtcccatgt catttttaaa tatggtttta gtggaggtat taatatcaca gctagccata 1200accctaaaga tgataatggt tttaaggttt atgatcatac tggtgcacag cttttagaca 1260cacaaacaaa ccaattgtta agtgatttac cttgtgttac atctatgcta gatttggaat 1320tacaaccaaa tccaaagttt gtccatactc ttgacaatga aaaggtttat aaaaactatt 1380tcagagagtt gaaaaaggtg ttggttatta acaacaacaa tttcaaagac attaaggtag 1440tttttagtgg gcttaatggg acttcagttt gcttaatgca acgcttttta aagtaccttg 1500gttatagcaa tattatcagt gttgaggaac aaaattggtt tgatgagaat tttgaaaatg 1560ctcctaactt aaatccagag tataaagata catggatatt agcacaaaaa tatgctaaga 1620aaaataatgc taagttaatt attatggcag accctgatgc tgatagattt gcaattgcag 1680agttaaataa taatcaatga cattattttt caggtaatga aacaggagca attactgctt 1740actataaact taatcataag gtttttaaat caccttacat tgtctcaact tttgtctcaa 1800cttatttggt aaataagatt gctaaaagat atggcgcttt tgtgcataga accaatgttg 1860gttttaagta cattggtcaa gcaattaatg agttatcaca aacaaacgaa ttagttgttg 1920gttttgaaga ggcaattggt ttaataacta gtgataaatt aaaccgcgag aaagatgctt 1980atcaagctgc tgcattattg cttgagattg ctagacattg caaagaacaa aacatcacgc 2040ttttagattt ttataaaaga attctttctg agtttggtga atatttcaat ttaacaatat 2100ctcatccctt taaagctact gctactgatt gaaaagaaga gattaaagct ttatttaatc 2160aacttataaa tgctaattta actgaagtgg ctggttttaa agtagttaaa gtccatcttg 2220ataaacaaac aaatatctta gagtttggtt ttgaaaatgg ctgggttaaa ttccgctttt 2280caggtactga acctaaattg aaattttact ttgacctaac taatggcact agagaggctc 2340tagaaaagca agctaagaaa atttataaat tctttgtaaa tttactcaaa ctcaacaaag 2400cttaaagaag tatagaaaaa tgattaatta aaatcaactg caaaagtggc cactaaggtt 2460gttttttcac tcttaccact tttaaatagg tttgacaagt cacttttaga aagttacttt 2520caagatggat tgaggttaat ccattatgat gtgatggacc aatttgttca taatactgct 2580tttaaaggtg aatatttgga tgaattgaaa acaataggtt ttgatgttaa tgtccattta 2640atggtggaac agatcatccc tcaaataaat ttttatcttt cacaacctaa tgtgaaaagg 2700atttcgtttc atgttgaacc atttagtttt gcaaagatta aagaactaat ccaactagtt 2760aaagaaaatg gtaaagaagt tggtcttgct tttaaattta caaccaattt acaactatac 2820caaccatttt ttacaaccat cgactttatc actttaatga gtgttcctcc tggtaaaggt 2880ggtcaagctt ttaacgaagc tgtttttaca aatttaaaga ttgctaacca ttacaacttg 2940aaaattgaga ttgatggtgg gattaaagtt aataacattg atcaaattaa agcctttgtt 3000gatttcattg taatgggaag tggctttata aaattagagc agtggcaacg tcaaaaattg 3060ttgcaaacaa tctaa 3075 10 11899 DNA M. genitalium 10 tttacagttttagcaataat aaaaaatctt tgaatattgc ttgagaccct tcatctccac 60 cattaaagaattccaacgtc taacttacct ttgcataaat aagaagttag acgttttgtt 120 ttatattaggcaaaataaga tgtcatttga tggaaaacta aaagcgcaat caatcttaga 180 aacttacaagaattttgatt gatcaaaatg taagttagtg attattcaag ctaatgatga 240 tgattcatcagacagtttta ttaaacaaaa acttattgct tgtaacactg taggagcaaa 300 aagtgaattaattaaactat ctaatcaaat aactcaagca gagttaatag aaaaaataat 360 tagtttaaatcatgatgtaa atgttactgg tatcattttg caattgccag tttatccaca 420 cttagataaaaactcactac tagaagcaat taatccttta aaagatgttg atggtttaac 480 aactaatcatttggctgaaa ttaaaccttg tatagttgaa gctataataa cactaaaaga 540 actatttaaccttgaattta ataatcaaaa aattgttgtg gtaggtttgg gaataactgg 600 tggcaaacctatttatgaat ttttaaaaac tagtggttat aaagttcaag catgcgataa 660 agatactccaaatacatttg aattgattaa aagtgctgat atagttttta ctgctattgg 720 aaaatctcatttttttcaag ctaaaaactt taaaaaagga gttattttat ttgatatagg 780 tgtttcaagaaacaagcaaa ataaactttg tggtgatata aatcctgaag gcattgaaaa 840 aaaagctagatgatgaacta aaacgcctgg cggtgttggc ccttttacag ttttagcaat 900 aataaaaaatctttgaatat tgcatgaaaa aaataaacgt tgtttacaat ccagcattta 960 ataaaaaagaagataaattg aaatcctaat tacaacttat catggatcta aaaaaacaat 1020 acattattgccttagatgaa ggtactagtt cttgtcgatc aattgttttt gatcacaatc 1080 ttaaccaaatagcaatagca caaaacgaat ttaacacttt ttttcctaat agtggttgag 1140 ttgaacaagatccactagaa atttgatcag cccaactagc taccatgcaa agtgctaaaa 1200 ataaagcacaaatcaaatct catgaagtga ttgcagttgg tattaccaat caaagagaaa 1260 caatagttttatgaaataaa gaaaatggtt tgcctgttta taatgccatc gtttgacagg 1320 atcaaagaactgcagcacta tgtcaaaaat tcaatgagga taagttaatc caaaccaaag 1380 taaaacaaaaaactggatta cctattaacc cctattttag tgctactaag atagcttgaa 1440 tcttaaaaaatgttccttta gcaaagaaac taatggagca aaaaaagttg ttatttggca 1500 ccattgatagctgattaatc tgaaaactaa ctaatggaaa aatgcatgtt acagatgttt 1560 caaatgcttcaagaactctt ttatttgaca ttgtcaaaat ggagtgatcc aaagagttat 1620 gtgatttatttgaagtacca gtttcaatct tacctaaagt tctgagttcc aatgcttact 1680 ttggtgatattgaaactaat cactgatcta gtaatgctaa aggtattgta ccaattagag 1740 cagttttaggagaccagcaa gcagctttgt ttggtcaact ctgtactgaa cctggaatgg 1800 taaaaaatacctatggtact ggatgttttg tactcatgaa cattggtgat aaaccaacac 1860 tctcaaagcacaatctgctc acaacagtag catggcaact agaaaatcat ccacctgtat 1920 atgcattggaaggtagtgtg tttgtagcgg gtgcggctat aaaatggtta agggatgcat 1980 taaaaattatctattcagaa aaggaaagtg atttttatgc agaacttgca aaagaaaatg 2040 aacaaaacctagtttttgta ccagctttca gtggacttgg agctccttga tgagatgcta 2100 gtgctaggggtattatctta ggaattgaag caagcactaa aagagagcac atagtaaaag 2160 ctagcttagagtcaattgct tttcaaacta atgatttatt aaatgcaatg gcaagtgatc 2220 taggctataagattactagc attaaagctg atggggggat tgttaaatca aactatttaa 2280 tgcagtttcaagctgatatt gcagatgtaa ttgtttctat ccctaaaaat aaagaaacca 2340 ctgcagttggtgtttgtttt ttagctggac ttgcttgtgg attttgaaaa gacattcatc 2400 aacttgaaaaactcactact cttgataaaa agttcaaaag cactatggac ccaaacataa 2460 gaaaaaccaaaattaacagt tgacataaag cagttgaacg tgctttaaaa tggaaagaaa 2520 ttgattaatcgttatcttga ttagacttta aattacactg gtgataatat ggcgataaga 2580 attaaaagtacaagagttgg tagatttgtt tctgaatcag tgggattagg tcatcctgat 2640 aaaatttgtgatcagattgc agatagtatc ttagaccaat gtttactaca gagtaaaact 2700 agtcatgtagcatgtgaagt ctttgcttct aaaaacctta ttttaatagg tggtgagatt 2760 tcaacaagtggctatgttga tgttgttcaa actgcttgaa gaattttaag aaatttaggt 2820 tacaacgagactgatttcag ttttttaagc tgtatcaaca accaatcact agaaattaat 2880 caagcagttttaaaaaataa tgagattaat gcaggagatc aaggcattac tgttggttat 2940 gcagtgaatgaaacaaagca actaatgcct ttaggagttt tactagcaca ctcgttttta 3000 aaacaagcagaaaaactaac aaaacaattt gattttttaa aaaatgatat gaaaagtcaa 3060 gtggttttaaactacagttt aaaccaagtt gaatgtgaag aagttttact atcaattcaa 3120 cacactaatgctattagttt aacagaattg agaaaagtga ttgaaaataa tgtaattcta 3180 cctgttttaaaccaatatgg ttttcaagat aaaaagccaa cttgtttagt gaatcctggt 3240 ggttcttttgttttaggtgg acctatggca gatactggac taactggtag aaaaatcatt 3300 gttgacacctatggtccata tgctcaccat ggtggtggta gctttagtgg caaagatcct 3360 agtaaggtggatagaacagg tgcttatttt gcacgtttta tcgcaaaaca tattgtaagt 3420 ttaggctgggccagtgagtg tgaagtcagt attagctgag tcttttcaaa acccaatcca 3480 caatctattactgttaagtg ttttaacact aacatacagt atgatgaagt gttaattaat 3540 agagttgtaaataactattt caactgatcg attactaaaa ttattgacaa gctaaaatta 3600 cttgattttgttaagtattc tgattatgca gtttatggac attttggtaa tgatctttca 3660 ccatgagaacagcccactga attggataaa ttagaatgct taatcaaaaa tttccattag 3720 ttcattttggacaaaaagaa atttttatgc taagataaaa atgctaaata accaacagat 3780 ccaccagagtgtactgatca atgaagtgat ccataacctc aatattaacc cttgtggtaa 3840 ctatttagatctaactgcag ggtttgcagg acacagtcaa aagatcttag aaaaactaac 3900 aacaggaactttaacaatta atgatgttga taaagaaagt attaattttt gccaaaagct 3960 tttttttaaaaacaacaacg ttgttattat tcacgataac tttgctaact tcccagttca 4020 tcttaaacaactatcaataa ccaagtttga tgggatctta atggaccttg gtgtatcaag 4080 ccatcaactcaaccaaccta atcgcggttt tagttttaag aatgatggac cgattgacat 4140 gcgtatggaccaatccaatc agaaaaatac cgcactaaca gttttaaaaa acttaactga 4200 acaaaagttaagtctaatcc ttaaaaagta tggtgatatt aaacacccta aaccaattgc 4260 tattggattgaaaaaagcag ttcaaactga aaaaaatctt accacaactc aactagcaaa 4320 agtggtaaaagaatgtgcta ctggatttga aaaataccaa tcaagaaact atcttgccaa 4380 agtttttcaagcaattagga tctatcttaa tgatgagatt actaatctga aaactgcgtt 4440 aacttttatccctaatcttt taaaaaacaa cagcaggttt cttgtgattg tttttcactc 4500 cattgaagaaaaaattgtaa ggaatttcat tgcaaaacta accagcttta tccaacctga 4560 agctctacccattaaactca ctcctgctta ccagttaatt acaaaaaaac caatcctacc 4620 ttcccaaaaagaacttgaat taaacccgcg ttcgcgtagt gccaaactct ttgttatcca 4680 aaaaaactagcggttttata caatgtataa cctgtctaaa agacaatttc atgctaattg 4740 ctatctgagcgatgacacaa gaaggactaa taggtaataa caacacttta ccttggatga 4800 ttaaacaagagctagctcac tttaaaaaaa ctacgttatt tcaagctttg ttaatgggga 4860 gaaaaacttacgaatcactc cccaaggtat ttgaaaaaag aacaatattt ctcctttcaa 4920 aagatcaaaactaccgtttt gaagaaaagg gaagtgaagt gaaagttatt aatgattttt 4980 gaccactaattaaaagttac caagcaaata aagaaaagga tttgtttatt tgtggtggaa 5040 aaagtgtgtatgaacagacc attaatgaat gtgatcagtt aattgtttca atcattaaaa 5100 agaagtataagggtgatcag tttttgaagg ttgatctcag taaatttgta cttaatgaag 5160 ttgtagagtttgaggaattt aatgttaatt attatagaaa gaaacaacaa taataaaaaa 5220 ccataaatcactaacaaaag ctttatatta acaatggttg ataaaaacag tttaagaaaa 5280 ttaatgcttctaaaaagagc agaactaaat gatcttgaaa aatcgcattt agatcaaaag 5340 attaaccaaaaattaatggc ttttttaata acaagaccaa caattaaaaa tttagcactt 5400 tacattcccattaaaaacga agtggctttt ttagataact ttctagattt tcttaagtta 5460 aataaaattacaagctgttt tcctagtatt gttgatcaat ttaacatgaa gtttattgat 5520 caaaataataatgaaattaa ccctaatgat attgattgtt tttttatccc tttattagct 5580 tttaataaggcaaaccacag gattggtttt ggtaagggtt attatgaccg ttatttatca 5640 ttaactagcaaaaaacaact aaaaataggg atagcatatg actttcaata tgcagaattc 5700 actaatgatccttgggatta tcaattagat ttaattattt gcaatggata acgattaaat 5760 aaagcttcataccgttgaag agatcttgat aatgcataac aagcaattgc ttttagcaca 5820 taggggttattcattcattg ctccagaaaa caccaaacta gcatttgatt tagcttttga 5880 atattgttttgatggaatag agcttgatgt tcatttaact aaagatgaac agttagttat 5940 cattcatgatgagacaacat tgagaaccgc attagttaat aaggaggttg agtttgaatc 6000 attagttagtttaaaaagag atgatcatag tgcttttttt caccttaaaa ttcaatttca 6060 atcgatcctaactttaaaag agttcttaga tctttattta gataaattta agttaatcaa 6120 tattgagattaaaactgatc aaaaaccata tttaggaatt gaaaagaagc ttgttgacct 6180 agttaaaggttatggtaaaa aagcaataga taagatcttg ttttcatcct ttaactttga 6240 atctttgcaaaaagtttatg atttagataa tagttacaaa aaaggttttt tattttggac 6300 taaaaaacagtttgaaacaa ttagtacagc tagaatccaa aagatttgtc aattcctcca 6360 cccatgaaccaaaatatatg aaaagtatcc ccaaatgatc aaaaaactta acttaccttt 6420 aaatttatgaacagtaaaca gtcaaaataa gtttcagcag ttcttagctg ataatcatgt 6480 ttatgcacaaattgctaaca aaaagtttga aataaaaata aattaggcga tattcaaaaa 6540 aattcttaaaccaaattaat aaaacaatga gtgttattga tatttttaaa aaacgattac 6600 aagctgttagtaaaaaacct gtaattatct ttccagaagg ttgatcagca agtgttttaa 6660 aagcagttgaaatgcttaat gaatctaagc tgatccaacc tgcagttatc tttcataatc 6720 gtcaggaaatccctgcaaat tttgataaaa aaataactca ttatgtgatt gatgagatgg 6780 atttaactagctatgctaac tttgtctatg aaaaacgtaa gcataagggg atggatttaa 6840 aagaagcacaaaagtttgta cgtgatccta gttctttagc tgctacctta gttgctctaa 6900 aggttgttgatggtgaggtt tgtggtaaag aatatgctac aaaagatact ttaagaccag 6960 ctttacagttactagcaact ggtaattttg tttctagtgt tttcatcatg gaaaaaggtg 7020 aagaacgtttgtacttcact gattgtgctt ttgctgttta tcctaactcc caagagttag 7080 caacaattgctgaaaacacc ttcaattttg ccaaaagttt aaatgaggat gagataaaaa 7140 tggcttttttaagctattca acgcttggca gtggtaaggg tgaaatggtg gataaagttg 7200 ttttagcaactaaactattt ttagaaaaac accctgaatt gcatcaaagt gtttgtggtg 7260 agctccagtttgatgctgct tttgttgaaa aggttaggtt acaaaaagca cctcaactaa 7320 cttgaaaaaatagtgctaat atctatgttt ttcctaattt agatgctggt aacattgctt 7380 ataaaatcgcccaaagactt ggagggtatg atgcaattgg tcctattgtt cttggacttt 7440 caagtccagtgaatgatctt tcaaggggag ctagtgtcag tgacattttt aatgttggaa 7500 ttatcactgccgctcaagca attaaataaa tcagagtaat tttattaata tttatctaac 7560 ttacatctggtgcgcttaag aaaagttaaa aacgctcttt taaaaattaa tcaaagtcct 7620 tatttttattcaaaagataa gtttgctaag tttactaaaa aacaattagt gctggaattg 7680 ggttgtggtaagggtacttt tttaatcaaa gaagcacaaa aaaataacaa ttttcttttt 7740 ataggaattgaacgtgaacc tacaattgtt ttaaaagcaa ttaacaaaat taacaagttg 7800 gattttaatttggaaaatat cttattgttg tgtacagatg caaaacaact tgatgattat 7860 tttcaagctgaatctgttca aaaaatcttt attaatttcc ctgatccttg acctaaaaag 7920 cgtcatatacaaagacgtct aacaagtcca gattttttga aacttttttg aaatttacta 7980 gtaaaaaatggcttaattga gtttaagact gataatgata agttatttga atatacttta 8040 acaacattgcaagaaaatag tcaaattttt gaaattatcc atcaaataac tgatcttaac 8100 aattctgaattcagttttca aaatagtatc actgaatatg aacagcgctt tatggaatta 8160 gaaattccaattaaaaaact agtgattaag aaaataattt aaaagactct tgaattatta 8220 gttaataataatatttattg atatggacaa atttttaatt gatgttattg tagaaatccc 8280 taaaaacagcaaaataaagt atgagtatga tcgtcaaact ggtcaaattc gcgttgatag 8340 aatcctatttggaagtgaat catatccaca aaactacggt tttattaaaa atacattaga 8400 ttgagatggggatgaacttg attgttttat ctttgcagat caaccatttt tgcctgcaac 8460 agttgtgcctacaagaattg taggagcact tgagatgatt gatgatgggg aaattgatac 8520 taagttattaggagttattg attgtgaccc tagatataaa gaaattaatc aaattagtga 8580 tttacctaaacatagaatag aagaaattct tatcttttta aaaacttata aattacttca 8640 aaaaaagactgtaattatta agggtttaaa agatgtttgt tgagctaaaa aagaatatga 8700 aatttgtttgcaattaatga aagattatgg tcatttatca aaagatcaat ttatccaaaa 8760 aatgcaaattcttcatccag aacattacca aaagtaatat tattttttaa taaataaggt 8820 aaatattcttcggttaaatg caaagtcaca aaatcttggt tgttaatgca ggtagcagtt 8880 caattaaatttcaacttttt aatgataaaa aacaagtact agctaaagga ctttgtgaac 8940 gtattttcattgatggtttt tttaagcttg aatttaatca aaaaaagata gaagaaaagg 9000 ttcaatttaatgatcataat cttgctgtta agcatttttt aaatgcgctt aaaaaaaaca 9060 aaattattactgaactttca gaaattgggc taatagggca tagagtagta caaggagcaa 9120 attattttacagatgcagtt cttgttgata cacattcact agcaaaaata aaagaattca 9180 ttaagttagcaccgcttcat aataaaccag aagcagatgt tattgaaatt tttctaaaag 9240 agataaaaactgctaagaat gttgctgtat ttgataccac ttttcacact actattccaa 9300 gggaaaattatctttatgca gttcctgaaa attgagagaa aaataactta gtaagaagat 9360 atggttttcatggaacttct tataaataca ttaacgagtt tttagaaaaa aagtttaata 9420 aaaaaccacttaatttaatt gtttgtcatc ttggtaatgg tgcaagtgtt tgtgcgatta 9480 aacaaggcaaatcactaaac acatcgatgg gattcactcc ccttgaagga ttaataatgg 9540 gaacacgtagtggtgatatt gatcctgcca ttgttagtta cattgctgaa cagcaaaagc 9600 tttcatgtaatgatgttgta aatgaattaa ataaaaagag tggaatgttt gctataacag 9660 gtagttctgacatgcgtgat atttttgata aaccagaaat taatgatatt gctataaaaa 9720 tgtatgttaatcgtgttgct gactatattg ctaaatacct aaatcaactt tcaggtgaaa 9780 ttgatagcttggtatttact gggggagttg gtgaaaatgc tagttattgt gtgcaattaa 9840 taattgaaaaagttgcttca cttggtttta aaactaacag taatttattt ggaaattatc 9900 aagatagttctctaatttca acaaatgaaa gcaagtatca aatttttaga gttcgtacaa 9960 atgaggaattgatgattgta gaagatgctt tgagagtaag tacaaacatt aaaaaataag 10020 ataaaaaacattactttaaa ttatatttaa tgatgcaaaa tgaataatgc taattttgaa 10080 aaatatgttgatttagtttt tgaagcaaac aaaaatttca acttaacagg atttaaaaca 10140 aaagaagctatttatcagaa tttagttata gaaatattga cattatttaa aggatatgaa 10200 aaattttttattgacaaaac tgtagcagac ttgggaagtg gaaatggttc gcctgggata 10260 atattaaaactgttatttca aaaaataaaa aagttagttt taattgatag taaacacaaa 10320 aaaattagctttttaaataa attaactaag caactaaatc tggagaaaac tgttgcaatt 10380 tgtgaacgaattgaagtaca taaaaatcac tatgatgtta tctgttctcg tggtctaagt 10440 acgattattaaagttaatga tttagcattt tccttgctta actcaaaagg tattattttt 10500 catataaaacaaagcttaga ccaatacatt gaatttgaaa aatcaaatca gaagaatcaa 10560 tttaacttgttatttataaa gcactttact agtcagaata aaaaactaat tttgatagct 10620 ttacaaaaaaatgattaaca atcaaaaaac accgttttta ttacgttaat taagttgaat 10680 gttttcaaaggtaagacttt tacttaataa agagttacaa cgtcaaagag aaaacatttg 10740 tttaattgcttcagaaaatt acgttagcca agacatatta gctgtaactg gttcagtatt 10800 aacaaataaatatgcagaag gctatcccag taaacgtttt tatcaaggct gtgaagttgt 10860 tgatgaatctgaaaacttag ccattgaaag ttgcaaaact ttatttggag cacaatgggc 10920 taatgtccaacctcattctg gatcatctgc taactatgca gtttacttag cattgttaaa 10980 accaggagatactatcttag gattagatct taattgtggt ggtcatttaa cccatggtag 11040 ccccgttaatttttcaggta agcaatatca agcagtaact tattcgttag attttgaaac 11100 agaaactcttgattatgatg caattcttca aattgctctc gaacacaaac caaagttaat 11160 tatttgtggtttttctaact attctaggac tgttgacttt aaaaaattta gtgcaattgc 11220 aaaacaagttaatgcgtatc ttttagctga tattgcccat attgctggtt tcatcgctgc 11280 aggtttgcaccaaaaccctt tgccttttgt ggatgttgtc acttcaacaa ctcataaaac 11340 tttgcgtggtcctagggggg gtatcattat gtctaacaac caagcaatta tcaaaaagct 11400 tgatagtggagtatttcctg gatgtcaggg tggaccttta caacatgtga tagcagctaa 11460 atatgtttgttttaaagaag ctttgaatcc aaagtttaag cagtatatgc aacaagttaa 11520 agataatgctttagcaatgg caaattgatt tttaaagcag ggttatcgtg ttgtgtcaaa 11580 aggtactgaaacccacttat tttcattagt ggttggtaat ggtaaagatg ttgcgttgtg 11640 gttacaaaaagctaacattg ttttgaatat gaatacaatc ccttttgaaa caaaatctgc 11700 ttttagtccttcaggtatta gacttggaac tcctgcaatg acaaccagag gttttaaaac 11760 taatgactttatttttgttg ccagtttgat tgataaggtt attaaaagta atggtaatca 11820 aaaggtaattagtcaaacaa aaacagctgt tttaaatctc ttaaaacgct ttccgctcta 11880 taagggtttagcttattaa 11899 11 15051 DNA M. genitalium 11 attaaaaaaa taccttgattttgacacaat caagtaattt atgaataaag gtgtttttgt 60 tgttattgaa ggagttgatggagcgggcaa aactgcttta attgaaggtt ttaaaaaact 120 ttatccaact aagtttttgaactatcaact tacttatact agagaacctg gtggtacttt 180 gttagctgaa aaaattcgtcaacttctttt aaatgaaaca atggaacctc taactgaagc 240 ttatttgttt gccgcagctagaactgaaca tatcagtaag ctaattaaac cagcaattga 300 aaaagaacaa ctagttatttcagatagatt tgttttctct agttttgcat accaaggatt 360 aagcaaaaaa ataggcattgatacagtaaa acagattaat catcatgcgt taagaaatat 420 gatgccaaac tttacctttattttggattg caattttaaa gaagcattac aaaggatgca 480 aaagcgtggt aatgataatcttcttgatga atttattaaa ggaaagaatg attttgatac 540 agttcgttct tattatttaagcttagttga taaaaaaaac tgtttcttga ttaatggtga 600 taataaacaa gaacacctagagaaatttat tgaattgtta acaagatgct tacaacaacc 660 cacgcattac taacaactaatttttagttt aaacttattt aaagataact aacgtgataa 720 aaaaagttca acatgctttaatcttgaatg aattgacaaa actgcgtgat aaaaatacaa 780 caacctccca gtttcgcatggccttgaatc aaatcacttc attactcttt tttgaagcaa 840 ctaaacagct accactagcaacagttgaag ttgaaactcc ctttgctaaa acaaagggct 900 acaaattaaa aaatgacattgttcttgtac ctattatgcg tgctggactt ggaatgattg 960 atgctattgt tcgctattcagataaaatca gagttggtca tttaggaatc tatcgtcaaa 1020 cccaaacaac cagtgtaatttcatactata aaaagatgcc tgaaaacatc tctgattcac 1080 atgttattat tcttgatcctatgcttgcta ctggaactac attgttaact gctattaaat 1140 ctattaaaga agataaacctatcaaaatta gtgttattgc tatagtagca gcacctgaag 1200 gaattaataa agtagaaaaaatgcatcctc atgttgatat atttcttgca gcaattgatg 1260 aaaagttaaa tgacaatagatacataatcc ctggtcttgg tgatgctggg gaccgtttat 1320 ttggtactaa ataatgtttttaatagagac ttttgcaaat cttgaccagg ttcaatggtt 1380 tgtcctactg ttttatctctaattgctttg atgaaatttt taacaacaag caggttaaca 1440 tcagcatcaa gcaatgcaattctaatctct tttagaacta actctacatc tttctcagtg 1500 atcgtttgag cgttaatttttttttgcatc gtgcgcataa cgatgcttga taacattgct 1560 ttgaacatga tttttaattatttattatta aataatgttt taataaaaca atattgcaat 1620 atgaccccac atataagtgctaagaaagat gacattagca aagttgtttt aatgccaggt 1680 gatccattga gagctaaatggatagctgag caattcttag atcaagctaa attagtcaat 1740 gaagtgaggg gaatgtttgcttatactggg cagtataaat ctaaaacagt tacagtaatg 1800 ggccatggaa tggggatcccttctattgga atttattcat atgagttgat gaatttttat 1860 gaggttgaaa ctatcattagaatcggaagt tgtggtgctt tagcaccgca attaaaatta 1920 aaagatcttg ttattgcttcaaaagcatga agtgagtcta tttatgctaa agacatgggt 1980 gttgaaattc cagaagataagatcttattt gcaacaagtt ctttagtgga attagcaaaa 2040 gaaactgcga ttaagaacaagcttgatttt catgaaggat tagtattttg tgaggatgct 2100 ttttatcaaa ctagaaaagatgtaattagt cttgctaaag aaaaaaatag tttagcagtt 2160 gaaatggaag cacatgcactttatgctaat gcaatcctgt tgaagaaaaa agcacttaca 2220 ctcttaacag tatctgattctctagtaact catgaagcac ttagttctga attaagacaa 2280 aagtcattta agcaaatggctttattagca cttgaaatga ctcaaaaact aatctaactg 2340 ctcaaaaaac aataattattaataaataaa aattcctatg aaggtgaatt tagagtggat 2400 aattaaacag ttacaaatgatagttaaaag agcatatact cccttttcta actttaaagt 2460 tgcatgtatg attattgctaacaaccaaac tttttttgga gttaacattg aaaattcttc 2520 ctttccagta actttgtgtgctgaaagaag cgccattgct agcatggtta caagtggtca 2580 taggaaaatt gattatgtttttgtttactt caatactaaa aataagagta actcaccctg 2640 tggaatgtgc agacaaaacttactggaatt ttcccatcaa aaaacaaagc ttttttgtat 2700 tgataatgat agtagttataaacaattttc cattgatgaa ttattaatga atggttttaa 2760 aaagagctaa acagcttatcagtttctgca atatatgaac gtcacattga atggtttgcg 2820 aacactttgc tgatggtgaaacttatatcc gttttgatga atcagttcgt aacaaagata 2880 tctatatttt tcaatcaacctgtcctaatg ttaacgatag cttaatggaa cttttaattg 2940 ctattgatgc attgaaaagaggtagtgcta aaagtattac tgccattcta ccctattatg 3000 gatatgcaag acaagatagaaaaacaaaag gaagagaacc aattaccagt aaattgattg 3060 ctgatatgtt aacaaaagcaggtgctaaca gggttgttct aactgacatt catagtgatc 3120 aaacccaagg tttttttgatattcccgttg attctttaag aacttatcac atctttcttt 3180 ttagagttat agaactacttggtaaaaaag acttggtggt tgtttcccct gattatggtg 3240 gggttaaaag agcaaggttaattgcaaata cactagaact accattagcc attattgata 3300 aaagaagacc atctcataatgttgctgaat caattaatgt tttaggtgaa gtgaaaaata 3360 aaaactgttt aatagttgatgacatgatag atactggtgg tacagtaatt gcagcagcca 3420 agctattaca aaaagaacaagctaaaaaag tgtgtgtaat ggcaactcat ggtttgttta 3480 acaatgatgc agaacaaaagtttatggaag catttgatca aaaactaatt gatttcttgt 3540 ttgtatcaaa ctctattcctcaatataagt ttaaagctgt aaagcagttt gaagtagttg 3600 atctagcatc tttatatgaagaggttgttc tgtgttacgc taacagctta tcagtttctg 3660 caatatatga acgtcacattgaatggatca aaaagcacgt ataaatagcc aatctggtta 3720 gcagctatcc caattcctggaataatgtca tattcttgtg ctttaccatc atatgaagca 3780 tcaacatatg caatcatctttttaatacag gtttcaattt gctcatctat tggaaaatta 3840 acagcttcag ttggcttgttaatcaaagca ttatcatcaa aaacaagcca agttttagtt 3900 ggttgaaaag tcattgataaaaacagtaaa gttaaaatta ttctaacaat tgaagtgaac 3960 aatcagggga gaatttttgtcattactggt cctagcggtg ttggcaaaag cacccttgtt 4020 aaagccttat tagatcatttcaaagaacaa ctgttctaca gtatctctgc aactacaaga 4080 aaaaagcgca ttagtgaaaaagagggaatt gattattttt ttaaagataa agatgagttt 4140 gaaaacttaa taaaacaagatgctttcatt gaatgggctt gctataataa ccattattat 4200 ggaacgctca agtctcaagctgaacaagca attaaaagcg gaattaattt aatgcttgaa 4260 attgagtatc aaggtgctttacaggttaaa agtaaatatc ctcataacgt tgttttaatt 4320 ttcattaaac caccttcaatgcaagagttg ttaaaacgtt taaaaaagcg taatgatgaa 4380 gatgaaacca caattaaaaaacgtttagaa caagctaaga tagagtttca acagattgat 4440 aattttaagt atgttgtcactaacaaagag tttgataaaa cccttaatga gttgaaatca 4500 atcttactat ctgagtttatttaaaccaac cttgattttg aaattttatt aggtatttta 4560 aaaaatgatt ggagcaaagactagggttgc aatagttggc gggattggtt acataggtag 4620 ttgttttgct agttttatcaaagaacaaaa tgataagcta attgttactg ttattgataa 4680 caacaaaaat aaccatgtaattaaactctt aaaaaagatt ggaattgaat tctattttgc 4740 tgatttacta gatagacataagctaactga agtaattgca gcaattcaac ctgatgtggt 4800 atttcacttt gctgctaaaacaagtgtaag tgaatcagta cataatccat tgaagtactt 4860 tgattgcaat gtaattggtactttaaacct aattagtgca attagtaact tacagaagcc 4920 aattaaatta tttttcgcttctagtgctgc agtgtatggt caaacaacta atagttacat 4980 tagtgaagag attgtaataactgaaacaca agcaaccaat ccttatggat tgagtaagtt 5040 tttagatgaa ttaatcttaaatgcagttgc caaaaatagt caactacaag ttgtttgctt 5100 acgctttttt aatgtggcaggtgcaattct gccatttggt aattttaatg gtaataccac 5160 gcttttaatt cctaacttagtaaaagcctt tttaaaacaa actccctttt ttttatatgg 5220 caatgattat gcaactaaggatggtagttg cataagagat tacatccatg tttatgatat 5280 atgtaatgct catttcttattatgaaagtg gttaaatgat catcgccaaa ttaaatttga 5340 aacctttaac ttggggagtgggataggaac ttctaattta gaagttattg atattgctaa 5400 aaaagtgttt tatcctagtagattaaattt agaaattaga ccaaaaagaa gctgagatcc 5460 agcaatttta gtagcaaatgttgctaaagc aaaacaaacc tttcaattca aaataacgcg 5520 taatttgaaa gatatgataagtgatgagcg taatttttat gagaattttt ataatgacgc 5580 ttattaacag tgcaaactagcaaaggtagt gtgaaaatta tcacctaatg gtagcacagt 5640 ttaataagtt cattatcttaggacccccag gggcaggaaa aggtacagtt tgtaaactgc 5700 ttagcaaaac aactaagttagtccatattg ctagtggtga tctgtttaga gaagccatta 5760 aaaaccagag tgttattggtagaaagattg cagcaattat cagtcagggt ggttatgttg 5820 atgatgccac tactaaccagcttgtttatg aatatatcac taccaatcca ttaccaaatg 5880 gttttatctt agatggttatccaagaacag agaaccagct tgattttcta aatattaaac 5940 taaccattga catggtctttgaactagttg ttagtgatct gaataaactg attacacgga 6000 ttgataacag ggttatttgtaacaactgta acagtgttta taacttgctt tttcaaaaac 6060 cactagttga aaatagttgtgatcagtgtt cagctaaact agtgaaaagg agtgatgata 6120 acaaagcagt ggtcaaagcaagaatggagt tatatcaaca aacaattcaa ccaatccaca 6180 cttacttttt caacaaacaacttttagtac aaattgattg ctttttacca ctagaagaac 6240 aactcaagac aatcaaacaatttattagat aacggtttta tacaatgtat aacctgtcta 6300 aaagacaatt tcatgaaacagtatttagat ttagctagtt atgttttagc aaatggtaaa 6360 aaaagaaaaa accgtacagatacagatact ttaagtgtct ttggttacca gatgaaattt 6420 gaccttacta atagttttcctttattgaca actaaaaagg ttaattggaa ggcaattgtc 6480 catgaattgt tgtgatttattaagggtgat accaacatta agtacttagt tgataatggg 6540 gtgaacatct gaaatgaatgaccatatgaa aactttaaaa aatcaccaag ttttcaaaac 6600 gaaacactcc aagaatttatcttaaaggtt aaaactgata atgagtttgc taaacaattt 6660 gctgatttgg gtcctgtttatggcaagcaa tgacgtaatt ttaatggtgt tgatcaactc 6720 aaaaaagtca tccaagagattaaagaaaat cccaactcaa gaaggctaat tgtctcaagc 6780 tgaaacccta gtgaattggaaaaaatggca ttggctcctt gtcattcact ctttcagttc 6840 tatgttgaag aagataaactaagcttacag ctttaccagc gcagcggtga tatctttctt 6900 ggtgtcccat ttaacattgcatcttacgcc ttacttgtgt atttagttgc tcatgaaact 6960 aagttaaaac ctggttattttatccataca ctaggagatg cacatatcta tgaaaaccac 7020 attgaacaaa ttaaattacaactaacaaga acaaccctag acccccctca agtggttttg 7080 aaaagtgata aatcaatctttgcttatagt tttgatgata ttgagttagt tggttataat 7140 taccatccat ttatctatgggagggttgca gtttaattaa tgttaattat tatagaaaga 7200 aacaacaata agagatatggcagctaacaa taaaaagtac tttttagaat cattttcccc 7260 acttgggtat gtaaagaataattttcaggg caacttacgt tctgtaaact ggaatttggt 7320 tgatgatgag aaggatttggaagtgtgaaa caggattgtt cagaactttt ggttacctga 7380 aaagatccct gtatccaatgacatcccctc atgaaagaaa ctctcaaagg attgacagga 7440 tctgatcact aagacctttactggtttaac actacttgat actatccaag ctaccattgg 7500 tgacatctgt caaattgatcatgctctaac tgatcatgag caggttattt atgcaaactt 7560 tgcttttatg gtaggggtacatgcccgttc ctatggaacg atcttctcaa ctttatgtac 7620 atcagaacag attaacgctgctcatgagtg ggttgtaaac actgaaagtc tccagaaaag 7680 agcaaaggca ttaatcccttactatacggg caatgacccg ttaaaatcaa aggtagcagc 7740 agctttaatg cctgggtttttactgtatgg tgggttttat ttgccttttt acttgtcatc 7800 aagaaaacaa ctaccaaatacatctgatat tatccgctta atccttcgtg ataaagtgat 7860 ccataactat tacagtggttataaatacca acgtaaacta gaaaaactcc ctttagcaaa 7920 acaaaaggag atgaaagcatttgtttttga actaatgtat cggttaattg aacttgaaaa 7980 ggactattta aaagagctttatgaagggtt tggaattgtt gatgatgcca ttaagttcag 8040 tgtttacaat gctggtaagtttttacagaa cttaggttat gactccccgt ttactgcagc 8100 agaaaccagg attaaaccagagatttttgc ccaactatca gcacgtgctg atgaaaacca 8160 tgactttttc tcaggaaacggttcgtcgta tgtgatggga gttagtgaag agacaaatga 8220 tgatgattgg aacttttaatttctttcaaa acagcaacta gtatttatag ttatccacta 8280 tgacatccaa agaaaaaatccctactttta atactgaaga agatgttgaa agttacattt 8340 cttttaatgc ccaagccaaaatctatgatg attttgcaat cgatttacaa gcagttgaaa 8400 gctatattca agagcatgtaaaacccaaaa ctaaggtctt tcattccacc aaagaacgcc 8460 ttgattttct gattaagaacgattattatg atgagaagat catcaacatg tacagttttg 8520 aacagtttga agagatcacccataaagcat attcataccg ctttcgttat gctaacttca 8580 tgggagcatt taagttctataatgcctatg ctttaaagac atttgatggt aagtactact 8640 tggaaaacta tgaggatagggtggtgatga atgtattgat gttagctaat ggtaacttca 8700 ataaggcatt aaaactcttaaaacagatta tccttaaccg ttttcaacca gcaaccccta 8760 cctttcttaa tgctggtagaaagaaacgtg gtgaatttgt ttcatgttac ctgttaagga 8820 ttgaagataa catggaatcaataggtagag cgataacaac tacactacaa ctatcaaaac 8880 gtgatggggg agtagcacttttgctttcca acttacgtga agcgggagcg cccatcaaaa 8940 agatagaaaa ccaatcatcagggattatcc caattatgaa attgttagag gactcttttt 9000 cctattccaa ccaacttggacaaagacaag gagcgggagc ggtgtatctc cattgtcacc 9060 atcctgatgt tatgcagtttttagatacta aaagggaaaa tgctgatgag aagatcagaa 9120 ttaaatcact ctccttaggacttgtgattc cagatatcac cttccaatta gcaaaaaata 9180 acgagatgat ggcacttttcagtccatatg atatctatca ggagtatggt aaggctttat 9240 ctgatatctc agtaactgagatgtattatg aattgcttga aaaccaacgc attaaaaaga 9300 cctttattag tgctagaaagttctttcaaa caattgctga actccacttt gaaagtggtt 9360 atccctacat cttgtttgatgatacagtta acaggagaaa tgcccacaaa aacaggatag 9420 taatgtctaa cctttgcagtgaaattgtcc aaccatcttt accttctgaa ttctattcag 9480 accttacttt taaaaaggtaggtagtgata ttagctgtaa cttggggagt ttaaatattg 9540 ctagagcaat ggaaagtggtagtgagttag ctgaattgat tcaactagca attgaatcac 9600 tggatttagt gtcaaggatcagtagtttag aaaccgctcc ttccattaaa aaaggtaatt 9660 cagaaaacca tgcgttgggattaggagcga tgaacttaca tggattttta gcaacaaatg 9720 ctatctatta tgattcaaaggaagcggttg attttactaa catctttttt tatacagtag 9780 cataccatgc gtttagtgcttccaataaat tagcattgga actaggtaaa tttaaagact 9840 ttgaaaatac taaatttgctgatggtagtt actttgataa gtacactaag gtagctagtg 9900 acttttgaac atgtaaaacagaaaaagttc aagccctttt tgataaatac caagtaaaaa 9960 ttccaactca ggaaaattggaagcaattgg tagcaagtat ccaaaaagat ggacttgcaa 10020 actcccattt aatggctattgccccaactg gatctatctc atatctctct tcatgtaccc 10080 cttcacttca accagtagtatctcctgttg aagtgagaaa agaagggaag ttaggacgga 10140 tttatgtccc tgcttataagcttgataatg ataactatca gtactttaaa gatggtgctt 10200 atgaactggg ctttgaacctattattaaca tagtagcagc agcccaacaa catgttgatc 10260 aagcaatctc tttaaccttgtttatgactg ataaagctac caccagagat ctcaataaag 10320 cttatattta tgcttttaaaaagggttgta gttctatcta ttatgtcaga gtaagacaag 10380 atgttttaaa agatagtgaagatcacacta ttaaaatcaa ggattgtgag gtttgttcta 10440 tctaataaaa ataaaccttaacccaacata ttaaaaagtg tttatatgca actaaaaaag 10500 ccccattttc aaccaaataaaattgctaat tgtattgtga tcgggggaat gattgcttta 10560 ggaaaaacca ccattgctaatacattagct aaccacattc aagctgcaaa agttgtttgt 10620 gaattggaaa ctaatgaccagttggttgaa cttttactag caaagatgta tgaacgtagt 10680 gatgaattgc tctattcacctttgtttcag ctttatttta cgcttaatcg ctttggtaaa 10740 taccagaaca attgcaacactatcaatcca accatttttg atcgttctat ctttgaagac 10800 tggttgtttg ctaagcacaacatcattcgt cctgcagtct tttcatacta taaccaactg 10860 tgaaatagat tagcaaaagaactagttaat aagcatgggg ttcctaattt atatgtcatt 10920 ttggatgggg attgaaaattatttgaaaaa agactattta tgcgtaaccg caaagtagag 10980 attgataact ttactaaaaatcaactttac tttcaaaatt tacacagggt ttacactgga 11040 tttatggaag cggtttgtaatgattttggg attaattact gtattataga tgcaaaacta 11100 ccaatagtaa ctattattaaaatgatcctt gaaaaattaa agttacaaaa gttagattga 11160 aaatttatct aattaattgcaggaattaac agtttttaaa aaaaagatat ttatggatca 11220 aaactttaag ttgcttgatcaagcaatcaa gcgctttgaa aattttccca accaaggtac 11280 attgttttat gacattaccccagtattttc caatccccaa ctatttaatt ttgtgctaac 11340 ccaaatggca cagtttattaaagctattaa tgcagaagcg atagtatgtc ctgaagcgag 11400 gggttttatc tttgggggagcattagcttc taaaacccaa ctcccgttag tattggttag 11460 aaaagccaat aaactcccagggcaattaat tagtgctagc tatgatttgg agtacagaaa 11520 acatgctgta ttggagatgtcaaccacttc attaatccaa gctaataatg ctaaaaggtg 11580 tgttattgtt gatgatgtacttgccactgc tggaacagtt gctgctattg accaattact 11640 taaacagtta aatggtgaaactgtgggata ttgcttttta attgagctga aaaaactcaa 11700 tggtaaagct aagttacaaccaaatgtggt tagcaagatt ttattacatt actagttttg 11760 attgttagtt ttgtttcatttgtttaaatt tagttatgaa ttgacaaata gcaattgatg 11820 gtccaagtag ttctggaaagtccagtgttg ctaaaaaaat agctgaagaa cttgattttt 11880 tttatttttc tagtggaaaaatgtatcgtg cctttgccta tgtaatgcaa gtgaatagat 11940 taaatattga tctttttttaaaaatcatta atcaaattaa ctgacgcttt gagaaagatg 12000 ctgtgtatta taacaatgctgatattacaa cagttattac aacccaatca gttgctaaca 12060 ttgctagtaa aatagctgttgatcctaaca ttagaaaaat tgcagttatt aaacaacaga 12120 aactagcaga aaataaaaacatagtgatgg atggtagaga cataggaaca gtagttttaa 12180 aaaatgctca attgaagttttttttagatg ctaaagttga aattagagcg cagcgaagat 12240 tacaagatat gggaatttctctatcaaatg aaaaaaaact aaaggaacta attcaagaat 12300 taaagcaacg tgatcaaattgatagttcta gaactgcaga cccattaaaa aaagcccagg 12360 acgctattta tcttgacacttctgaactaa gttttgatgc agtagtaaaa caaaccctca 12420 aagaagcaaa gaaggtttttaaactttaat aaaaactcaa taataaacgc tttaaaatat 12480 ttcactttga tggatgaaaaagggatttta gttgcaatta gtggtggtag ttgctcagga 12540 aaaactactg ttgctgaaatgatttatcaa cttttaagta aaaaattaaa agttgcgatc 12600 atctgtcaag ataactattacaagtcctat aaaaataagc cattattaaa aagaaaaaca 12660 ataaactttg atcatcctgatgcttttgat tgaaaacttt taagatcaca cattgaagat 12720 cttctaaacg gtagtatagttaatgttcct ttatatgact acattaacta taccagagct 12780 aaaaaaacag caaaaattggtccaattgat gttgttattc tagagggttt aatgccatga 12840 tttgatgaaa aattatcaagactttctaag ctaaaaatat ttatagaaac aaatggggaa 12900 gaacgtttaa ttagaagaatagaaagagac tgacaaaggg gaagaaatat tgattctatt 12960 attaaacagt gacgcgaaatagtagcacca atgtatgaaa tatttgtaga aaaaatgaag 13020 cgaaatgctg atttaattctgccttgaagt caacgcagag aagtaagtac aagtgtattg 13080 gatgtcgcaa ttgaacacttatttcacaaa actgttgaaa aaaataatta gaagtgcttt 13140 actaagtgca attagttgtcctagtttagc agtgcaaatt ctttcacagc aaactattga 13200 taaagctttt gaagagaatgactttgtcat tttttcaggt ggcactggta atccttattt 13260 ttccactgac actgcattagctttaagagc agtgcaaaca aaagcagttg ctattctgat 13320 tggaaaaaat ggtgttgatggtgtttatac agctgatcct aaaaaagata aaaatgcaac 13380 ctttttacca acactcaactatgaccatgc cattaaaaat gatttgaaaa ttatggatat 13440 tactgctttt actatgtgtaaggaaaataa tctgaaaata attattttta acattaatgc 13500 tgagaatgca ttattagatgcattaaacaa aaaaggtcgc tttactataa ttgaaaataa 13560 ctaatgttgt taattttaaataagtttaag ataagctgga gataatgaaa acaaaaataa 13620 gaaaagcagt tattcctgctgctgggttgg gtgttaggtt actaccagca acaaaagcaa 13680 ttcccaaaga gatgttaccattggtaaata aacctactat ccaatacata gtagaggaag 13740 cagttaaaag tggcattgaacagattcttg tcattgtttc atccaaaaaa acagctatat 13800 tagatcattt tgattatgatctgatcttag aaaatgcctt aattcaaaaa aataaattgc 13860 aggagcataa agagattgaagatattgcta atttagcaca tatctttttt gttagacaaa 13920 aaaatcaaga tggtttgggagatgcaatct tgtttgctga atcttttgtt ggtaatgaag 13980 actttgcagt attgttaggtgatgatgttg tttttagtaa agaacctgct ttaaaacaat 14040 gcttggaagc ttattatgaaactaattgtc aaacaatcgg tgtacaagaa gtagatcctt 14100 gtcatgttga taagtatggaattatcaccc ctgaaggtga ttacaaaaat aaagatctta 14160 ttaaggtttt agcaatgactgaaaaaccta aaccaaaaga tgctaaaagt aatttagcaa 14220 tcttagggcg atatgtactcaaaccatcta ttttcaaagc acttagaagt gtaccttatg 14280 gagttggtgg tgagttgcaactaactgatg gtttaaattt ttgtttgaaa aatgaaaact 14340 tttatgcaag aaagtttactggtactaggt ttgatgttgg cacaaagagt ggttttatta 14400 aagcaaattt atttactgctttaaacaata aagatattag taaaaaagaa gttttagaac 14460 ttttaaattt agttaaagcttaattagctg ttgttttagt agaacgtcaa aaaactaaat 14520 aagatgggta ttaaatctattgttattaat gaacaacaga tagaagaagg ctgtcaaaaa 14580 gcagttaatt ggtgcaatgctaaatttaat aataaaaagg taattgttct tggcattcta 14640 aaaggttgca tccctttccttggcaaagtg ataagtaaat ttagttttga cctccaacta 14700 gattttatgg cagttgcttcttatcatggt tcacatgtac aaaaacaacc acctaagatt 14760 gtgcttgata tgtcccatgaccctaaagat aaagacatcc ttttaataga agatattgtt 14820 gatagtggta gatctattaaattagttatt gatcttctaa aaacaaggca tgctaaatca 14880 ataactttaa ttagcttaattgaaaagatt aaacccaaag cctttgatat taatattgat 14940 ttttcttgtt ttaaagtaaaagataatttt ttggttggct ttggtcttga ctatgatggt 15000 ttttatcgta acctaccttatgttggtgtg tttgaaccag acaatcccta a 15051 12 4055 DNA M. genitalium 12ggaaaagatt gatttgtgtg gttctagaaa taaagcatag atgttaagtg cagggatagt 60tggtttacct aatgttggta agtcaacttt atttagtgct attactaatt tgcaagttga 120aatagcaaac tatccttttg caactataga acctaatact ggcattgtta atgttagtga 180tgagagatta gataaattag ctagcttaat taatcctgaa aagatagttt atacaacctt 240tcgttttgtt gatatagcag gtcttgttaa aggcgccagt caaggtcaag gattgggtaa 300tcaattctta gcaaacatcc gtgaagtgga tttaatttgt catgttgtaa gatgttttca 360agataaaaaa attgttcatg ttaacaatac aatagatcct gtttttgatt ttgaaattat 420tgttaatgaa ctaatccaag ctgattttga attaataaca aacagaatcg gcaagcttaa 480aagaaaagct gaatcaggtg ataaaatcgc taaagaagag tttgtattac ttgaaattgt 540tttaaatgga ttaaaacaag gtcaaatgcc cattcagact ctaagtgaaa gtgaattgaa 600aacaattaaa tcacttaatc tattaacagc taaacctatt ctaatagtag ccaatgtatc 660tgagaatgac ttattaaacc ttgataataa tgaagcttta aaaaaattga atgcttttct 720tgatcaaaaa aagattccca aggcaatcac agtttgttct ttaattgaaa aagaattaag 780cggtttgaaa ttagaacaac gtcaatactt tttggatgaa cttggcttaa aaaattattc 840aggtttaaac cgagtaattc aagctgcata tcaaacttta aacctttggt ctttttttac 900ttttggtaaa aaagaagtta gagcatgaac atttaaaaag ggttgaaatg ctcctcagtg 960tgctgggcaa attcattctg attttgaaaa aggatttatt aaagttgaag taattagttg 1020agatcaattg tttgcaatga aatctttaca agaagctaaa aaacaaggtt tgataagatt 1080ggaaggcaaa aattacttaa taaaagatgg tgatgtttgt aactttaaat ttaacgtcac 1140ttaagcttta gttcacaaaa aaattttcga attattcgtt gaagatggat gcacattttt 1200tgaagagtgc aagtgattta aaagattgtc ctcaagataa tatcccagag atttgtttca 1260tgggaagaag taatgttggt aaatcaagtt tgattaatgc tttttttaaa aagaaactgg 1320ctaaaacttc agcaacacca ggtcgaacac aattactaaa ttactttgaa tataaagaca 1380aaagatttgt tgatttacca ggttatggct ttgctaaaat aaacaaaaat aagaaagatt 1440ttattactaa tttacttacc caatttttaa attttcgtag taatctagtt ggtgttgttt 1500tgatagtaga tagtggagtt gttactgttc aagatcagga agtggttaaa attattttgc 1560aaacaggatt gaactttttg attgttgcta ataaatttga caaactaaat caaagtgaaa 1620gatatttttc gcttaagaat attgcaaatt ttttaaaagt taattttgat aaatgtgttt 1680ttgcaagtac aaaaacacat cataatcttg ctttagttca caaaaaaatt ttcgaattat 1740tcgttgaaga tgaaagataa ggtgatatta ttttctttga tggttgtgaa tttgtaatta 1800cagaaatcgt ttttaaaata aagaaaaaga aaccaaaata atggctatta cagattattg 1860tgagtgtcgc tttactgctg gaaatggtgg taatggaatc atagcatgaa aaagagaagc 1920acattatgat aaaggtggtc ctggtggtgg taatggtggt aatggtggta atgttatttt 1980gcaagctgat cataactgcg attcactttt tttcttgaag aataaaaaac acctgtttgc 2040agaagatgga caaaatggta aaccagattt agcacatggt aaaaatggtt cagatctttt 2100aattaaagtg ccaataggaa caacagttaa aaacttagaa aataatagtg tattggtgga 2160ttttgttcat gataaacaga gttttatttt gtgttttggc ggaaaaggcg gaaaaggaaa 2220tgctgctttt aaaagcccaa ttatgcgtgc tcctaatcta tatgaaaatg gtgataaagg 2280agagatttta aacgttagtt tggaagttaa atatttagct aatgtaggaa ttgttggttt 2340tccaaattca ggtaaatcaa cactaatctc caaactttca aatgccaaac ctaaaattgc 2400aaactatcgc tttactactt taatacccgt acttggtgta gttaaatatc aaaataatag 2460tttagttttt gctgatattc ctggtttgat tgaaaatgct agtgaaggaa gtgggttagg 2520acatgatttt ttacggcata tagagaggtg tgaaatatta attcatttaa tttcacttga 2580tcctgtagat aatgatgatc cttgcaaagc atatttacaa ataatggatg aactttcaaa 2640atattctccc cttctagtta aaaaaaagat gcttgttgta gctaataaaa ttgatgttaa 2700tgaaggtgag aaacggttta aaaaattaga aaaatttctt caaaaaaaat ctatttctgt 2760attaaaaatt tctgctttaa agaaagaatt aggcaattta cttgatagag tttttgaact 2820ttacaataaa acaatttccc aatttggagc taataagttt agtttgccaa tggaacttga 2880gaagcattat gtttttcaaa ataccaatga aaataataac gaccctttaa atattgaaaa 2940agatagttta aacagatgaa ttgttaattg taaacgtcta agatattgat ttgataaaat 3000tccacaaact acgcttgata acattcgtcg cttaggaaat aaaattaaag aaatcggtat 3060tgaagatcaa ttaaaatccg ttggtgctaa aaaaggtgat attattttct ttgatggttg 3120tgaatttgta attaatgact aatgtttttt caagatgcaa ttcatgaaga gatcttatca 3180gtatgaaagt tttaaaagtt ggtgttttag gacctactaa tgcaggaaaa tcaacgctaa 3240ttaatttttt acataacgat gatagtctga tggtatcatc catgaataac acaacgcttc 3300tttctatttc cactgaggta attaaccaag ctaataaaaa tattgttttt attgatgtcc 3360ctggttttac tgagaaaaaa cattcaaatt atgaattaat aactaaagaa attcgcaaag 3420cattaagtgg aattgatgta ttacttttag ttgttagaag tgatcagaat aacaagatag 3480aatttttaaa aactcaatta caacaattaa agcgctatca aaatttaaca agaatttttt 3540taattaataa atttcatcaa aaaagtttaa gtgaagttaa taaagcaatt attttagaag 3600agtttaaacc acaaaaaaca attgaaataa acttgcttaa gtttgataaa aacctctttt 3660gatcaatttt taaacaagtt gaacttaggt ataatatctt tcgtaaagat atcaatttta 3720ttgatgcaaa caacgatgac tttaagattc ttgaaggatt acgtgaacaa ataatttttt 3780attgcaaaaa cgaaattccc catatagcaa gaattgaaat tattgaaaag agtttcaata 3840aagaaaaaaa cttgttaaaa attcacctag taattagtgt tccaaaatta agccaaaaaa 3900agattatcat tggaaaaaat gcagaaatga tcaaagcaat tgggatagca actcgcaaaa 3960aactattaaa tcattttgac tgtgatattt ttattgatat ttttgtaaaa acagaaaaac 4020aaaaattgcc tgtttatagt tttctttcta aataa 4055 13 31241 DNA M. genitalium13 accaagttct tgaaagattt taaagagatt aattacttca atggaaggaa gttgaagtta 60taaattactt tatgtttttt tgtgtatagt tcttggtatt ttatatggaa ttgctaaccc 120tatcttatta gcacaaggtc ttggttttat ttttcctatt actagtagta atggtcgtgc 180tgttgactca atatattcat taatttaccc aacaaattta aatgtattca ttaggctcac 240aattgtgagc gtaactgttt ttgtagctta tgcattaatc tttgtattta atgtagcgca 300aaactatgta gggattaaac tttaccaaca aacatgtgct actttgcgtt gaaaggcata 360tttaaaaatg cagagtatgt caaccagctt ttttgatacg caaaataatg gtgatcttat 420gagtaggtta actaatgata tgtataacat tgataaccta ttcactcaag ctggtggaca 480agctattcaa agtttgttta atattttaac aacctcagta ttaatatttt tattaagccc 540agttattgca cttatttcac tttcaatttt agctacatta attacttttt cttttgcctt 600tctaaagaaa tcaaaaactt catatagtca agtacaaaat aatttgggtg atatgtctgg 660ttatattgaa gaggttttaa ctaatcataa ggttgttcat gtcttgaagt tgcaagagat 720aatgattaag gattttgatc aatacaacaa atcaatgatc aaaccaactg taagagggaa 780tacatattcg atctttcttt tttcttggtt tggttttata tcaaatatta cttatctggt 840ttctatatca attgctactg cttttagtgt taattctatt ccttcatttg gaattagtgt 900tattaactat tcattcatgt tgtcttacat tgcttcttta aggcaaataa ctttagcatt 960agatcaaatc tttacccttt gaaacttagt tcaattaggg gttgttagtg cagaaagagt 1020atttaaggta ttagatctta atgtagagaa agatactgct actattgaca aattacctga 1080tattaaaggt aatataaggt ttgaaaatgt agcatttggt tacaataaag ataaacctac 1140tttaacagga attaacttta gtgttaaaca tggagatgta gttgcaatag taggtcctac 1200aggagctggt aaatcaacta ttattaatct attgatgaaa ttctataaac cttttgaagg 1260aaagatttat atggataact ttgaaattag tgatgtaact aaaaaagcat gaagagaaaa 1320gatttctata gtattacaag attcattctt atttagcggc acaattaaag aaaatattcg 1380tttaggcaga caggatgcta ctgatgatga gattatcgct gcatgtaaaa ctgctaatgc 1440tcatgatttc atcatgcgtt taccaaaagg atatgacact tatatttcca ataaagcaga 1500ttatctttct gttggtgaaa ggcaattatt aacaattgcc agagcagtaa tccgtaatgc 1560tccagttttg ctcttagatg aagcaactag ttcagttgat gtccattcag aaaaattaat 1620tcaagaatca ataggaaggt taatgaaaaa taaaacttct tttataattt ctcatcgtct 1680ttcaattatt cgtgatgcaa cattaataat ggttattaat gatggtaaag tacttgaaat 1740gggtaatcat gatcagctga tgaaacaaaa tggattttat gcacgtttaa aacaatcttc 1800ggttcgttaa ctttggtaat ggtgcagttg cccaagttaa tttaaagaag atggctacaa 1860gtgaaacaaa agccaagttt ttaacagttg cacttacttg aggaataggt gttttatttg 1920gtgttttaac tgctaatgct atctttaagg gtagtggtca tttaaaccct gctatatcat 1980tattttatgc aattaatggc agtatcaaat cacctactgc attaatatga cctggttttg 2040taattgggat tttagctcaa ttcttaggtg caatgatagc tcaaacaaca cttaactttt 2100tattttgaaa acaactatca tcaaccgatc cacaaacagt tctagcaatg cattgtacaa 2160gtcctagtgt atttaacatt actaggaatt ttctaactga atttattgca actttaatat 2220tgataggtgg agttgttgct gctagtcact ttcttcataa caacccaaac tctgttcctc 2280ctggatttat ggggctttga ttggttgctg ggattattat tgcttttggt ggcgctacag 2340gctccgcaat taatcctgca agggatttgg gaactagaat tgtgtttcaa ttaactccaa 2400ttaaaaataa ggatgcgaat tgaaagtaca gctgaattcc agtaattgct cctttatctg 2460caggattagt tttatcaata attattgggt tttcccctgc acctgttctt taaatactaa 2520ttaacgtttt ttattgaaaa ttaagtattt aaattgaacg aacattcttt aattgaaatt 2580gaaggtttga acaagacctt tgatgatggt tatgtttcta taagagacat tagcctaaat 2640attaaaaaag gcgaatttat tactatttta ggcccttctg gttgtggtaa aactaccctg 2700ttgaggttat tagctggatt tgaagatcct acttatggca agatcaaagt taatggtatt 2760gacattaaag acatggcaat ccataagcgt ccttttgcga cagtttttca agactatgct 2820ttattttccc atctaactgt ttataaaaac attgcttatg gtctgaaggt aatgtgaaca 2880aagttagatg aaattccaaa acttgtaagt gattatcaaa agcaacttgc tcttaagcat 2940ttaaagctag aaagaaaaat agagcagtta caaaaaaaca attctaatgc tcaaagaata 3000aagaaattaa aggaaaaatt acaaaaactt ttagaaatta acaaacaaaa agttattgag 3060tttgaaaata aagaaaaact acgtagagaa gatatttaca agaatttaga gcaattaaca 3120aaagaatggg atctactttc tcaaaagaaa ctaaaagaag ttgaacaaca aaaacaagca 3180attgataaaa gttttgaaaa agtagagaat aaatacaaaa aagatccttg gttttttcaa 3240cacagtgaaa tacgtttaaa acaatatcag aagaaaaaaa ctgagttgaa agctgatatt 3300aaagcaacaa agaacaaaga acaaatccaa aaattaacta aagaacttca aaccttaaaa 3360caaaaatacg ctaataaaaa agcaattgac aaagagtatg acaaattagt tgtagcttac 3420aataagaaag actattgaac ttcttattga gaaacataca cacttcaaca aaaagaagct 3480tttgaaaaac gttatctttc aagaaaacta actaaagctg aacaaaataa aaaagttagt 3540gatgttattg aaatggttgg tttaaaaggt aaagaagatc gtttgcctga tgaattatca 3600gggggaatga aacaaagagt tgctttagca cgttctttag tagtagaacc tgaaattctt 3660ttattagatg aaccattatc tgcacttgat gcaaaggtta gaaagaattt acaaaaagaa 3720ttacaacaga ttcataaaaa aagtggattg acttttatct tagtaactca tgatcaagaa 3780gaggctttag ttttatcaga tcggatagtg gttatgaatg agggaaacat cttacaagtt 3840ggtaatcctg ttgatattta tgactctcct aagactgaat gaattgctaa tttcattggt 3900caagctaaca tctttaaagg tacttattta ggagaaaaaa agattcagtt acagagtggt 3960gaaatcattc aaactgatgt tgataataac tatgttgtag gtaagcaata taagatctta 4020attcgtcctg aagactttga tcttgttcct gaaaataaag gtttttttaa tgttcgtgtt 4080attgataaaa actacaaagg attgctttga aagataacca cacaattaaa agataacact 4140attgttgatt tggagagtgt taatgaagtt gatgtaaata agacctttgg tgttttattt 4200gatcctatag atgttcattt aatggaagtt taacaagatg cacattaaga aaaaatactg 4260acttctgctc cccttctttt tattaatgac aatcttcttt attattccaa tggcatggat 4320tattgttagt ggattacaaa gtgaagatgg ggctagtatt agtcaaaaat atgaaccact 4380tgttagtggc ttaggttttt ttaacagttt ctgaaccagt ttgtggatct caatagtgac 4440tgtaattgtt gcattgttgt tttcttttcc tttttgttac tttctctccc aatcaaaaaa 4500caaaattttt aaagcgtttg ttatttcaat tgcaacagtt cctatttgaa gtagttttct 4560tattaagtta attggattga aaaccctact tgatttatta attggacttt ctttaaacag 4620agttggtgat aacaacttaa cttttggttc aggatatacc ttacttggaa caatttatct 4680gtttactcct tttatgtttt taccacttta taaccacttc tgtgttttac ctaaaaactt 4740gttgttagct agtcaagatt tgggttataa ctggatttac agctttgtga aagtagtaat 4800tcctttttct aaaaccgcaa tgttatcagg aattgcttta acttttttcc ctgctttaac 4860ttcagttgca attgctcagt ttttagataa ctctaaccaa gccgaaaccc ttggtaacta 4920catatttacc ttgggtaata atggttatga tagtgcaatt gaaagaggca gagctgctgg 4980agcaattatt attgctgctt taattacttt tgcaatttac tttactgttg tttttttgcc 5040taaaattgtc cgtattgttc ataacaaatg aaaacaacat gaaaaagcat tttaagaatt 5100taattaaaaa cagttatttc tttctgttaa taactttaat ctatttacca cttttaatag 5160ttgtacttgt tagtttaaac ggttcttctt caagaggaaa tatagtgctt gattttggta 5220atgttttaaa tcctaatcct gattctaaat ctgcttattt aagattaggt gaaactgatt 5280ttgcaacacc actaataaat tcaatcatta taggtgtgat cactgtttta gtgtctgttc 5340ctattgctgt tatcagtgcg tttgcgcttt taagaacaag gaatgcttta aaaaagacaa 5400tctttggaat tactaatttt tctttagcaa ctcctgatat tattactgct atctctttag 5460tgttgttatt tgctaacact tgattaagtt ttaaccagca gttaggtttt tttaccatta 5520ttacttccca tatctctttt tcagtgcctt atgcattgat tttgatttac cctaaaattc 5580aaaaattgaa tcctaattta attcttgctt ctcaagattt aggctattcg cctttaaaaa 5640cttttttcca tattactcta ccttatctaa tgccaagtat tttttcagca gtactagtag 5700tatttgcaac tagttttgat gattatgtaa ttacctcttt agtacaagga tcagtaaaaa 5760ctatagcaac tgaactctat tcatttagaa aaggaattaa agcatgggca atcgcctttg 5820ggtctattct catattgatt agtgtcttag gagtctgttt aataaccctg caaaagtatt 5880taagggaaaa aagaaaggaa ataatcaaaa taagacaatg aaaaaacagt taaaatattg 5940ctttttctca ctttttgtta gtctctcatc aatattgagt agttgtggtt caacaacatt 6000tgtactagct aactttgaat cttatatttc gcccttattg ctagaaagag tacaagaaaa 6060acatccctta actttcttga cttatcctag taatgaaaaa ctaattaatg gttttgctaa 6120caacacttat tcagtagcag tagcatctac ttatgcagtt agtgaattga tagaaaggga 6180tctattatca ccaatagatt gaagtcagtt taatctgaaa aaaagtagta gttcaagtga 6240taaagtaaat aatgccagtg atgcaaagga tttgtttatt gattcaatta aagagatcag 6300tcaacaaacc aaagatagta aaaacaatga attactgcat tgagcagttc cttattttct 6360tcaaaactta gtgtttgttt atcgtggtga aaaaattagt gaacttgaac aggaaaatgt 6420ttcatgaact gatgtaatta aagcaattgt gaaacacaaa gatcgcttta atgacaatag 6480gttagttttc attgatgatg ctagaacgat cttttcactt gctaacatcg ttaatactaa 6540caacaattca gctgatgtta atccaaagga agatggaatt ggttatttca ctaatgtcta 6600tgaaagcttt caaagacttg gattaacaaa atctaattta gatagtatct ttgttaattc 6660tgattccaat attgtgatca atgaattggc aagtggtaga agacaaggag gaattgttta 6720caatggtgat gcagtgtatg ctgcattggg cggtgattta cgtgatgaat tgagtgaaga 6780acagattcct gatgggaaca actttcacat tgtgcaaccc aaaatttccc cagttgcttt 6840agatcttttg gttatcaata aacaacaatc taattttcaa aaagaagcac atgagatcat 6900ttttgatctt gctttggatg gtgctgatca aactaaagaa cagttaatta aaactgatga 6960agaattgggt actgatgatg aagactttta cttaaaagga gcgatgcaaa actttagtta 7020tgtgaactat gtttcaccat taaaagtaat atctgatcca agtactggaa tagtcagttc 7080caaaaagaat aatgctgaaa tgaaaagtaa acaaatgtca actgatcaaa tgactagtga 7140aaaagaattt gattattaca ctgaaacact taaagcatta ttagagaaag aagatagtgc 7200agaattaaat gaaaatgaaa aaaaactagt tgaaaccatt aagaaagctt acactattga 7260aaaagatagt tcaattcggt gaaaccaatt ggtcgaaaaa ccaatttctc ccttacaacg 7320tagtaattta tcgttatctt gattagactt taaattacac tggtgataat gaacaaaatt 7380aagattgaca aggaaatcaa aaactcctaa tggatttttt ctctttaaac aaaatcataa 7440aacccaacca gaaattcact agtaatgaag ctgaatttct acagatagct actgattatt 7500tggaggaaag tcaaaactat cttcaaaagg gtttaaagca attaaaaaaa gaatataaaa 7560gatccattat ttataaccct aaccttgaat ataaacgctt tgttaaatga aaagaaaatt 7620tcactgaaac atttgaaagt tattatgaca ggttttttat taccaaatac aaccattatt 7680cactaagctt actttttagc tttattaatg aacagattga aacagttatt gctagttaca 7740actcatttct aaatgagcat aataagttag cttttaataa agttagtttt agttttgaaa 7800agaaactttt tgaagctaca caacagttta ataacttaga aaaaaacact gctattagtg 7860atgatttacc gctccagttt aaagttagaa caactcaact aaaagcccaa agagaaaggg 7920aattgaagaa cttgttgaat aaaatcaagc ttaaaaattt aagtgaaaaa aaacaagaaa 7980ttttgttaaa taactggttt aatagcaacg aacgtttgtt tttaaaaaat gaagtgaaaa 8040aggttaattg actaaactcg ccaagacaaa aacaacaagc agctcaaatt gatgatcaaa 8100acattattga attgaaaaat gtgtataaat acatcactaa tggcattact acaaatgcag 8160ttcttaaagg agttgatctt gccattaaaa gtcatgattt tattgtgatt ttaggccctt 8220caggatctgg taaaaccaca ttactaaaca ttatttcagg gatggataga gcttctagtg 8280gtagtgttat tgtcaatggt tataacatga tttgtttaaa tgatagaaag ctcactaaat 8340tccgtcaaaa gtatgttggt tacatctttc aacaatacgg tttattacct aatttaacag 8400ttagagaaaa cattgagata ggagcaaatc ttcaaccaga tcctagtaaa aggatcagca 8460ttgatgcact tttagaagcg gttgggatgg atagtttgca aaagaagctt cctaatgaat 8520tgagtggtgg gcaacagcaa cgtgtttcca ttgcaagagc ttttgctaaa aaccccttat 8580taatttttgg tgatgaacct actggggcac ttgatcttga gatgacccaa attgttttaa 8640aacagttttt agcaattaaa aagcgttatc aaacgacaat gattattgtt acccacaaca 8700atttaattgc taacttagct gatttagtta tctatgtagc agatggaaaa ataaaatcac 8760tacacaggaa cttaaatcct aaacaggttg aagagatcca ttgattaaac attaaccgtc 8820aacaacaaga aactttatag agcagtgaac agttgaacag gacttagtga acaagcggca 8880attaaaagtc gtcaagaaca tggtgctaat tttcttcctg agaaaaaagc tacccctttt 8940tggttgttat ttcttcaaca atttaaaagt ttagttgtta ttcttttact gctagctagc 9000ttgttatcgt ttgtagttgc tattgtcagt ggtttgagaa gtaactgaaa ctttaaccat 9060gatctgatta ttgaatgggt tcaacctttt attatcttat taactgtttt tgccaattca 9120ctaattggtt ctatccagga atttaaagcc cagaaatctg ctagtgcttt aaagtccttg 9180acaaagtctt tcacaagggt ttttaggaat ggtgaattaa ttagcattaa tgttagtgaa 9240gttgttgtag gagatattat ttttgttgat gcaggagata ttatccctgc tgatggcaaa 9300ttactacagg ttaataactt acgttgtttg gaaagctttt taactggtga atcaactcca 9360gttgataaga ctattgatag caatgaaaaa gctactattc ttgaacagac aaacttagtt 9420ttttcagggg cacaagtagt ttatggtagt ggcgtttttc aagtggaagc agttgggatt 9480aaaacccaag ttggaaaaat tgctaaaact gttgatgata gtgtaactaa actctcaccc 9540ttacaacaaa aactagagaa gataggaaag tgatttagtt ggtttgggct tggtcttttt 9600gctgtagttt ttcttgtcca aactgcttta ttaggatttg ataatttcac taataactga 9660tcaatagctt taattggtgc tattgcgctt gttgttgcaa ttatccctga agggcttgtt 9720acttttatta atgtgatctt tgcattaagt gtgcagaaac taactaagca aaaagccatt 9780attaagtatt tatcagtaat tgaaacactt ggatcagtac aaattatctg tactgataaa 9840actggtactt taacccaaaa ccagatgaaa gttgtcgatc acttctgttt taattcaaca 9900acccaaactg atctagcaag agcattgtgc ttgtgtaata atgcttctat ttccaaagat 9960gctaataaaa caggtgatcc tactgaaatt gctctcttgg aatgaaaaga tcgcagtcaa 10020ttagatttaa aaacctatta cagggtttat gaaaaagcct ttgattcaat cagaaaactt 10080atgacagttg ttgttcaaaa agacaaccgc ttcattgtga ttgttaaagg tgctcctgat 10140gtgttattac cattatgtaa taacgttcaa aatgaagtaa agaacattga aaacttactt 10200gatcaaagtg ctggtcaagg cttgcgtacc ttagcagttg ctttaaaggt tttatataag 10260tttgatcaaa acgatcagaa gcaaattgat gaacttgaaa acaaccttga attccttggg 10320tttgttagtt tacaagaccc accaagaaaa gaaagtaagg aagcgatttt agcgtgcaag 10380aaagctaata taaccccaat aatgattaca ggggatcatc ttaaaactgc aactgtaatt 10440gctaaagagt taggcatttt aactttagat aatcaagcag ttttaggtag cgaactagat 10500gaaaagaaga tcttggatta cagggtattt gctagagtaa ctccccaaca aaaattagcc 10560attgttagtg cttgaaaaga agcgggattt acagttagtg ttactggtga tggggtgaat 10620gacgcacctg cattaatcaa gagtgatgta gggtgttgta tggggattac tggggttgat 10680attgcaaaag atgctagtga tctgattatt agtgatgata atttcgctac tatagtaaat 10740ggtattgagg agggtagaaa aactttttta acttgtaaac gagttttatt aaacctgttt 10800ttaacttcaa ttgcaggaac agttgtagtt ttattaggac tattcatctt aggacaagtt 10860tttaaaacta atttattaca acaaggtcat gactttcagg tgtttagtcc tacccaactg 10920ctaattatta acttgtttgt tcatggtttt cctgctgttg cattagcagt acaacctgtt 10980aaagaaaaat tgatggtagg tagtttttct actaaaaatc tgttttacaa ccgccaggga 11040tttgatttaa tctgacaatc actattctta agctttttaa ctttattgtt ctatagctta 11100ggaattatat atgcaattaa taaccgtgat ttacaaacta gcggggatct aattaatcgt 11160gctggatcaa cgtgcggttt ttttattttg ggtgctagtg ctgctttaaa ctcattaaac 11220ctaatggtag ataaaccatt gcttatgaca aacccttggt tttttaagtt agtttgaata 11280ggttcacttg cttctatact ggtattttta ttgatcatct ttatcaaccc tttagggtta 11340gtgtttaatg tcttgcaaga tttaactaat cacccagttt taataagcta tagttttggg 11400ggagttattt tgtatatggg gatgaatgaa gttgttaaac ttattagatt aggttatggc 11460aatatttaac ctgaaaaaaa caggttcttt ttttatttct atttagtaaa tgttcaagta 11520tattcttaaa cgattaggac tagcagtagt tgcgatgttt atcgtaatgt ctatagtctt 11580ctttttagtg aacgctactg gtaatgttcc cttgtcagcc acttctgcaa gagatattgc 11640tgcagtgcaa gcacaactac aagagtttgg gtttaatgac cctattatag ttaggtattt 11700tcgctattga gctaagctat tttcctttca agctgatgct ttaggaattt attatgcaaa 11760ccctaaccaa acaattggtg agattgtgtt tgcaagagta ccaaatacct tatatgtggt 11820tttaatctct tttttaattg gttcattgct agggatcttt ttagggatgg tttcaggatt 11880gaatagaggg aagtttttag atgcagcaat taatgtgttg gtagttttat ttgtatctat 11940tccttcattt gtagtgggat tagggttact taaactagca ggatttttaa atctaccacc 12000acggtttatt aactttgatg atgctttttt tagctttgat cgtttcttgc ttgcatcaat 12060tatcccgatc ctttcattgg tcttctattc atcagctgct tttacataca ggattagaaa 12120tgaggtggtg gaagtgatga atcaagacta tattaaaact gcaaaaagta agggacttgg 12180gatgtttgct gtagctaggt atcatatctt tagaaactcg attattcctt ctattccctt 12240gtttgtattt ggaatctcag gtgctttttc aggtggattt attattgagt ctttgtttgg 12300agtacaaggg gtatctagga tcttaattga ttcagtgcaa gttaatgaaa ctaacatggt 12360aatgtttaat atcttgttta tccaagggat tcccttatta gcaagtgtct ttattgaatt 12420tatctatgtt ttagttgatc ctagaattag gattgcaaat agttctaatg ttagcttatt 12480aactaagtta aagttcttaa gttcaagaca ccaatggtta atgaagtgaa acaagattaa 12540cagtgataat gcccaaaata ttgtgtttaa ctcgccactg caccaccagc tattagaact 12600caatgcaatt gattacaaaa caaaaacagt tcaactaaca actgaacaaa aaactgctct 12660caatatcagt gcaactgcta actttatctt acttggtaac aagtgtttaa aactcaaaac 12720aatccatgga tagaaataaa agttttgacc ctaacttatt taaaagggtt gatatcaact 12780tattaaagcg aaatgatcag cttattggta aaccaactac caattcaata gaaattatca 12840agcgcttgtt tcaaaacaag tgggccatct tattttttct tttaatagtt gttattgtgc 12900tattagcaat tattgtgcct ttaacttccc ctttttcagc agtaactcct gtttcaacca 12960atgccttagc acaaaatcta ccaccacggt acttatggca taaaccaggt gacattttag 13020ttcataagat tacagcaaga tcaattgctg aaatctctca agctagtgga gttttagtag 13080gaacattacc tagtgcaaat agtaatccct tagcaactaa tgtccagtat gatattgctc 13140cttttcaact ccaagaattg cgtaattatt tccctttatt ggggactaat ggacttggga 13200ttgatatttg aaccttgttg tgagcttctg ttgccaagtc attgtgaatt gcagtagtag 13260tagcaattat agcaatggtg tttggaacca tttatggagc ggttgctgga agctttgttg 13320gacatatggc tgataacatt atgagtagga tcattgagat tattgatata gtcccttcta 13380ttctttgaat tattgtctta ggagctacat tccgctttgg tggggttaaa caatttgatg 13440atagtgttgt aatctttact ttaatctttg tgttttgaac atgacctgct actacaacca 13500gaatttacat tttgaaaaac aaagatacag agtacatcca agcagctaag accctagggg 13560cacaccaaat cagaattatc tttgttcata tgttacctgt tgtatttggg agattagctg 13620ttgtgtttgt tagtttaatc ccagcagtta ttggttatga agcttcctta gttttccttg 13680ggttaaaacc agctactgat attggcttag gggcactttt aaaccaagta acttcaagtg 13740ataatgtagc tttaatctta agttcgattg ttagctttgc agttttaaca gtagcagcta 13800gaacatttgc taatgcttta aatgatgcaa ttgaccctag ggttgtaaaa cgataaaatg 13860gcacttaaaa gaagtaattt ctttgttgat aaagaccaac aactaaagga taatttgatc 13920ttagacatca ctgatttaca tgttaacttt aaggttaaag atgggatctt acatgctgtt 13980agagggattg atcttaaggt agagaggggt agtattgtag ggattgtagg tgaatcaggc 14040agcggtaaat cagtgagtgt taaatcaatt attggtttta atgacaatgc acaaactaaa 14100gccaaactga tgaactttaa aaacgttgat attaccaaac taaagaaaca ccagtggaag 14160tattatagag ggacatatgt ctcttatatt tcccaagacc cattgttttc tctaaaccca 14220acaatgacga taggaaaaca agtaaaagaa gcgatttatg tggcttcaaa aagaaggtat 14280ttccaagcta aatcagactt aaaatttgct ttatcaaata aggagattga caaaaaaact 14340tataaaagta aactaaaaga gatcaaacaa acctaccaac aaaaaataaa acctatcaat 14400gtagagaaaa aaaccttaga gatcctgcag ttcattggta ttaatgatgc caagaaacgt 14460ttaaaggcat tcccaagtga gttttcagga gggatgagac agagaattgt gattgctatt 14520gcagtagcaa ctgaacctga tttaattatt gctgatgaac ctactactgc acttgatgta 14580actattcaag ctaaggtatt aactttaatt aaacaactcc gtgatctact taatatcact 14640attatcttta ttagtcacaa tatctcttta attgctaatt tctgtgactt tgtttatgtt 14700atgtatgcag ggaaaattgt agaacagggt ctggttgaag agatctttac aaatccactc 14760catccctata catgggcatt gatttcttca attcctgaac agaaagataa aaacaaacca 14820ctaacttcta tccctggagt tattcctaac atgttaaccc caccaaaggg tgatgctttc 14880gctagtagaa accaatatgc tctagcaatt gactttgaat accatccacc cttttttgaa 14940gttactaaaa cccataaagc agcaacttga ttgctgcatc cccaagcccc taaagttgaa 15000ccacctcaag cggttattga taacattacc ttaaccaaaa aagcactgca atttaaagat 15060caataatgga aaaccaaaac acaaaaaaac cacttgttaa tgttaaggct ttgagcatga 15120tgttcaaggt cagaggaact ctttttaaag cccttgatga aattggtttt actgttaatg 15180aaggggactt ctttggggtt attggtgaga gtggtagtgg taaatcaacc acgggaaaat 15240gtttgattag attaaacatt cctagtggtg gaaagattga gattgccaac cacttactct 15300caggaaaaaa acttactaaa gagaataacc agtggttaaa acaaaacatc caaatggtgt 15360ttcaagaccc ttattcatct attaacccta ctaaaaatgt gctaactgtg atttcagaac 15420cgctggtaat tagtaaaact gtttttgggg aaacaaaaca atacttaaag agtttgcaaa 15480agctctcttt taaagtaaag aaaacattgt taaggaatga tattgaactt gaaaccaagt 15540ttcacaataa cttttttaaa accgttatta agcaaattaa tgaatcattg tttaactttg 15600aagatcttga ttacaaggat ttaaaaccat cacatttaag gcaaagaatc ataaatgaaa 15660cagataaatt cattgaaaaa attagaagtg agtttgccct tttttatgat ttttatgcta 15720accaatcagt acccttgcaa aaggcattag atgatgcgaa ttcctcttta acaccatcta 15780gtgttattga gttaaaaaac cagttaaaag cattacaaaa acaagcaaag atttcaaagg 15840cagcatggga tattttacaa gccctaaagc aaaaccaaaa ggagttgaaa gattatgaaa 15900attatgtcca ttttgaactc caaaaaaagc cacgaatcta tcttaatacc tgacttttaa 15960caaccaaaag ctacattaaa gattccaagc aaaacatgca gcttactgat gatatctttg 16020ctttttcata taacagtatg gttgacaaga aaagaaactt ggttttaatt ctttctaaat 16080actataagct gttaccttat ttctatgacc aatcagtatt tgataatgct gatcaatttg 16140atgaaattgc taaccttatc ttttttgatt tagttgaaac attgcttggt gtaactagtt 16200tatttaatga tgcattagca gctgataaag tcccactaat taagtttgct aagttcttaa 16260ataagttatg tgacttgcgc tttttaacct taaaaaagag ctttaaaaaa acaagagtaa 16320gttgtagctt tagttttaac agtgaacctg aaatcttgtt tgccaacagc tgctatgatt 16380tgcaacaaat gcctcaaatc attaaaccct tttgagagaa gctttttaat gaacagaact 16440accaaaagat tattgattca gtttcaagac tgaatgtaat gattgcaaat tacattacca 16500aagcttttga aattaaaaaa actattgatg aaaaactaag ggagtttaaa caacaaaatt 16560tagctttaaa aaaagcttat tcagctaaca agaaaagtga ggcaaacaaa gcttccatta 16620atgagttaaa agtcaattta aaaacactta aaaaacagct taaacaagag aaaaatacta 16680ctaaaaaaca atcaaaaaag gaattaaaac cacttttaaa agaacaccat actgctttaa 16740aactccatga tgagtttaac catgatttac gcaagtggtt caaaaaactt aactttatgg 16800ttaagaaata caaccgactg gaaaacagcc agaaaaagtt ttgtttagtt aaaaagttaa 16860aagcgctttt caaaaaacag gatgaaacac tgcaaagtga attaagacca aaactaaaaa 16920catttggtgt aattaacttt gagtacaaac gtgcagtcaa agagtccaat gtctttcgat 16980tggtgcattt tgctaaaaat atctttaaac cattcttgtt ttttaacctc accaagattt 17040ttatgagaaa taaggtctat gaagcacttg atagtgttgg tttaaaaaga gaacatgctt 17100acagataccc ccatgaattt tcaggcggac aaagacaaag aattgctatt gcccgtgctt 17160taatcactaa acccaaactg attattgcag atgaattgat tagtgcactt gatgtttcta 17220tccaagccca agttattaac atcttgaaag acttggctaa aaaacacaac ttaactgtgc 17280ttttcattgc ccatgattta tcaatggtgc aaactgtttg taaccgtttg atcattatgc 17340ataggggcaa gattgttgaa cggggcagtg tggatgagat cttttcaaat ccagttcatc 17400cctacacccg ttccctaata aaagcatctc ctaagttaag caaaatcaat gttgatctcg 17460cttcttttga tgaaaacttc acttatgata gtgattattc actaaccaat atgccctttt 17520atattaaagt tcctaacagt gaagaacatg aactttactg tactcaaaag caatttgata 17580gttgaatcaa agaggctacg ccgataaatt aaagaatttt tataatgacg cttattaagt 17640ggtgtttaat taatggaaaa agttgccttc aaaatggagc atatctccaa aagttttgac 17700aatggcaaaa ttaaggctaa tgttgatgtt agcttagttg tttatgaaaa tactgtccac 17760accattttgg gggagaatgg tgcaggaaaa tcaaccctga cttcgatttt atttggttta 17820tataaacctg atagtggcaa gatctttatt ggtgaaaagc aagtaaattt taaatcttct 17880aaagatgcag taaaacataa aatcggaatg gtgcaccagc actttaagtt aatagaaaac 17940tacacggttt tagataacat cattctaggg aatgaaagta ggtttgggtt tttaccttta 18000attaatcgta aagtaagtga agcaaagatt aaaaccatca tggaaaaata tggaatcttt 18060gttgatctta aacaaaaagt tagtaactta acagtaggtc agcaacaacg ggttgagatc 18120ctaaaggttt tatttcgtga tagtaatatc cttatctttg atgaacccac tgcagtttta 18180agtgatcttg aaattcaaaa ctttctcaag attattgcta actttaaaaa gctaggaaaa 18240acaattgttt taatctctca taaattaaat gaaattaaac aagttgctga tacagctact 18300gtcttaagac ttggcaaggt agttggtagt tttgatgtta aaacaacacc agttgataag 18360attgcgcttt taatgatggg caaagagtta aaacaaacta aaaacaccac agattttgtt 18420gctaaagatg aacctgtttt aaaagttcaa aacctgaatt tgtttctcaa taaatcttta 18480gcatacaagt tcttagtgag gtgcaataac atccataaag cccaacaaat taagaaaaat 18540aaaccattaa aagacttatg gataattagt tttttaaata aactaaccac cagtaacaaa 18600acccctaaat tagtaaaagg cttgattaat aagttaggac tttcctatca agaaaataca 18660gatgaaacca ttagttttgc tatccataag ggagaaattt ttgctattgc tggggttgag 18720ggtaatggtc aaagtcagct tgttaattta atttgtggaa ttgaaaaagc tgctagtaat 18780aagttaattt ttaacaatat tgatatctca agatgatcaa ttagaaaacg gattaatgct 18840gggattagtt ttgttttgga agatagacat aaatatggct tgatcttaga tcaaaccgtg 18900aggtttaata cggttaataa ccagattaat aaccgtcctt ttagtagttg aaacttttta 18960aaaccaatgg agattgctct ttatagcaac actattatta aaaagtttga tgttaggggc 19020agtgctgagg gtagtgctgt tgtaagaaga ctttcaggtg gtaatcaaca gaaactaatt 19080attggtcgag aaatgaccaa acaaaatgac cttttggtgt tagcacaagt aaccagaggc 19140cttgatattg gtgctattgc ttttatccat gaaaacatct tattagctaa agctaataat 19200aaagctatct tattggtttc atatgaactt gatgagatct tagcacttgc tgatacagtg 19260gctgttatca ataaggggag aatagttggt atgggaaaaa gagatttaat ggatcgccaa 19320tcgataggta gattaataat gcaataaaag actatgacaa tgtggcaatt taaaagttac 19380tttaaacacc acctggtgtt ttgaaaagac cgatttttac atagctctga gaaacaaatg 19440caaagaagaa gtatcctctc ttcagtggtt ttgataatcc tctcttttct tatatcgttt 19500ttactgatta tttcaattcc tggaggtaga ggtgcgagct tctttgcact gtttactaag 19560ttatttttag ataacactaa tactgaaaat ttcttaagac agattgctat ttatatccta 19620gctggattag catttagttt ctgtatgagt gttggtattt tcaacattgg tatctcaggg 19680cagatgatgg ctggagccat ctttgggttt ttaatgattc tcaaggtgtt tccaagttca 19740tttcgacctg gttttggagg tcagattatt actgtattat tgatggtaat aggtagtgtt 19800agtgtggcag ttgttgttgc aactttaaag atttttttca aggttaatga agttgtaagt 19860gcaattatgt tgaactgaat tgtagtgctt attagtgctt atttagtaga gacttacatt 19920aaagataata gtgggggtac agcccaattc ttttccttac cactccctga tgaatttgct 19980ttatataact tctctccttt aacaaaaaag tttggttgat tagcttcact tattattgct 20040ttcattagtg ttattattgt ggcagtagta ttaaaataca cagtttttgg acacaaatta 20100aagtcaattg gcagtagtgt atttggttct caggcaatgg gttttaatgt tagaaaatac 20160cagttcttat cgtttattat ctcaggaatt ttatcaggac tattagcaac ggttgtttac 20220actgcatcaa ctgaaaaagt attgacattt aacaatgttg gggatagtgc tatttcagca 20280gtaccagcta ctggttttga tgggattgcg attggtttaa ttgctttaaa taaccccttt 20340aggattgtta ttgtttctgt tcttattgct tttgttaaca ttggggcaag acctgctaat 20400ttaaacccta atactgctag tttagtttta ggaatcatga tgtattttgc tgcactttat 20460aacctaatgg tttactttaa accatgaaga tacctagtga agctgaacat tggaaagata 20520aatctcacca catatgaaac atatgaaaac aaactagctg ctaacctaga gtgactaagt 20580ttccaacgct tcttgtcaaa acagaaaaaa aagaatgaca aaactaaatt taattggttt 20640gatactagtt tatttgaaca atatgcaaaa aacaaacaag aaattgttca agaataccat 20700cacaattgtg caactaattt aattgcttgg tgattgaatg caatccaaag tggcaatatt 20760aaaccttcaa ctacttttaa gttggaattt gttaatttta aacaccaaca gaagtttgta 20820ttaaattggt ttaaaaatga aagtgaatca ctgcgtgatt tccaatcaca gtttgagaga 20880atcaataagt tagtggaaag ggagtttgtt aagtaaaaac taggtaggat aacccaaaga 20940aaataattaa aatattgtga aaaaaaagat agtcccaatt aaccctttaa aagcagatga 21000gattttagca gttagtcact tatcatgtgt ttttaacagt aaaactaaca atcccattaa 21060ggtgattgat gatttttcct atacctttca aaagaaccaa atttactgta ttattggtga 21120tagtggcagt ggtaaatcaa cccttgttaa ccacttcaat gggttgataa aacccaacca 21180aggtgatatt tgggttaaag atatctatat tggtgctaaa caacgcaaga ttaagaactt 21240taaaaaactg cgaaaaacta tctcaattgt tttccagttt cctgagtacc aattgtttaa 21300agataccgtg gaaaaagaca ttatgtttgg tccagtagca ttaggtcaat ccaagtatga 21360tgcgcgccaa aaagcggctt attatctgga gatgatgggg ttaaaatacc cttttttaga 21420acgtaatccc tttgaattga gtggggggca gaaaagaagg gtagcgattg ctggtatact 21480tgcaattgaa ccagaaattc taatctttga tgaaccaact gctgggcttg atcctgaagg 21540ggaaagggag atgatgcagt taattaaaac tgccaaacaa caacaaagaa cggtatttat 21600gatcacccac cagatggaaa atgtccttga ggtggctgat gtggttttgg ttttagctaa 21660gggtaaacta gtaaaagctg ctagtccata tgaagtgttt atggaccaaa ctttccttga 21720aaaaacaacg attgttctcc cccctgtgat ccaagtgatc aaagatctaa ttgcgattaa 21780tgctcacttt aataagttaa ttgagttgca accaaagaac ctagaacagc ttgcatcagc 21840aattaacaag actatagcaa accatggata aatgtaaatt tagctaacaa gcttaactgg 21900ttgtttttga gatggctaac aataagagtg caattgagtt gaaaaacatc gttgttgatt 21960ttggtgaatc agttgcgatt gacaacatta accttagtgt tgaaaaacac caactagtta 22020gcttacttgg tcctagtggt tgtggtaaaa ccactacact tgcagttatt gcaggactta 22080ttaaaccaac tagtggtcag gtgttattta atggttatga tgtcaccaaa aaaccacccc 22140aagaacgtaa actagggcta gtttttcaaa actatgcact ttatccgcac atgaatgtgt 22200ttgaaaacat tgttttcccc ctctacagtg ataactcgtg aaaacaagca gttttggaaa 22260aaaacagtgt tgcaaaccat gagattaact gtttgttact tactagcaac ggtgcatcag 22320ttcaagagat tgatcagctc aataagttat ttcatgatag tattgaaaaa cccaaacaga 22380tccaatacca aattaatgac cttaatgtta gtgtttttaa aaacttaaat gaactaactg 22440caaaccttaa gttaatacca agtaagcacc agtttgctat taccaatctc aacaaacaaa 22500ctctaaaaca gattaatgaa ctggaagctg agtttaaaac aaagtgaaag ttacaaaaac 22560aaaccccaat taagagtggg gttgaacaca atgccaaact ccaagcaatt aaacaacact 22620ttagttatga aaaacaacgg ttaaaaaaac actatttcaa aactaaagtg gaactaaaac 22680aaacccttgt tgaaaacctt aagttagtta aaaaagcgat tagtgaacaa actaagttaa 22740ttaaacagag tagtgattac actaagttaa agcaattaaa acggttaatt aaagttgaac 22800ctaaccaact caaaaaacaa tataaggttt ttctcaatca gttaattaaa aactattcac 22860ttaaaactga taagttaact gatactcaac ttaatgaaat tgaacagatt aaaaccagaa 22920ttgtttcaat aaaacagttt atcaacaaaa ctgcacttga agtagctaac aaactagcga 22980ttaccaagat tttaaccaaa cgccctgata agatttctgg tggacaacaa caacgcgtag 23040caattgctag agcaattgtc agaagaccta aactattgtt aatggatgaa ccactctcta 23100acttagatgc aaagctaagg gtacagacaa gacagtggat cagacagttt caacaggagt 23160tacaaattac cactgttttt gtcacccatg accaggaaga agcgatgagt attagtgatg 23220tcattgtttg tatgtcaact ggaaaagtgc agcaaatcgg cacacccagt gaactttatt 23280taaaacctgc taatgagttt gttgcgcgct ttttaggcac ccctgagatg aacatcattg 23340aatgtagtgt caaaaacaac cagttgtttt gaaacaacca tctgttagtt actgagagtt 23400ttaagcttaa tgtagagaaa ctcttagttg ggtttaggta tgaacaacta gtggtcacta 23460ctaacaaaag tagtttgcaa gctaaactaa ttaacattga aaacttaggt aaacacttag 23520ttgctaccat tagtttgttt gataccacct tatcaatgcg cttagaattg aatagccact 23580taaaagtagg tgatagttta aatttcatta ttaaagctaa caacctccat ttttttgata 23640ttgatacaaa acaacggatt gagatttaac ttaagataat tgaaacatta aataagataa 23700ttacaagcta tgaatcaagc tagtgcaatt gccattttgg tcatttttag cctagcttct 23760ggttatctgt taggttcaat tatttttgct gatattttca gcaaaatact caagaaaaac 23820gtcagggaat ttggttcaaa aaacccagga gctactaact caatgcgtgt ttttggctta 23880aaaattggtt ttttggtggc tatttttgat gcatttaaag gtttttttgc ttttttatta 23940acctgaattt tattccgttt tggtttacaa ggttatttaa cagaaaaagt gtatcaaagc 24000acctattttt taagttattt aagttgtttt gcagctacaa taggtcatat ctttccgctg 24060tattttaagt ttaagggtgg taaggcaatt gctactactg gtggatcttt acttgcaata 24120tctttatgat gatttttaat ctgtctttta atttggataa tgattacttt aataactaag 24180tatgtttctt tagcaagtct tattacattc tttgtgttag ctgtaatcat cttaataccc 24240tgacttgatt atttatactt ctttaacagt gatcctctaa agtcgattac ttatcaaaat 24300gaatggtata tcattttatt tttttgcttg tgatattgac ctttaactgt ggttgttttc 24360tgattacacc gtgcaaacat aatcagaatt ttacatggta aggaaagcaa gattactcaa 24420ctaaattaat gatgtttgta aaaaagcgat ctttgattac tttagttaat tggtagttga 24480tgcaaacttt cattattact tcccctgttt tcaatccgta ttttaatgca gctttagagg 24540agtgattgct aactgaattt agaaaaaatg agttagttaa ggtcatctac ttttggcaga 24600acgctaacac tattgtggtg ggaagaaacc aaaatactta tgctgaggtt aacttaaagg 24660agttggaaag tgataaggtt aacttgttta gacgtttttc aggcggggga gcggtgtttc 24720atgaccttgg taacatctgt ttttctatta ttttgccaag aacaggtaaa gtgatggaaa 24780atgcttatga acaaactaca agaaatgtgg tgaagttctt aaatagctta aatgtacctg 24840ctgtatttca tggtcgtaat gaccttgaga ttaataacaa gaagttttct gggttagctg 24900aatatatcgc taaagacagg ttattagtcc atggaacatt attgtttgac actgactttt 24960ctaagttagc aaagtattta aatgttgata agaccaagat agcaagtaag ggtgttgaca 25020gtgttgctaa gcgcgttgtt aatgtaaagg agtatttacc aaattgaaca acagcaaaat 25080ttttagaaga gatgattaat tttttcactg ttactgaaaa agcagaaaca attgttttaa 25140ctaaagatgc actagcaaag gttgaaaaaa gagcaaaaga acactttcaa tcatgggagt 25200gaaactttgg taaaacttat gaatacaact ttaaaaacaa gcgttatttt aataatgctg 25260gtttatttga gtgcaatgtt caagtagaga aaggaacagt tgttgatatt aagttttatg 25320gggacttttt aagtgttgtt gatatcaccc cagtaacaaa aaaactaatt ggtcagaagt 25380acgattataa aacctttgaa aaactcttca atgaacttga tcattttagt gattactttg 25440gcagtttaaa acctgagcaa ctcttaggag taatatttga taacaagtaa cttaaataat 25500aaatctttat aatttttact agatttacta atgcaaacgc atgaaattct tttaaaaatt 25560aaagaaattg ctaaatcaaa aaactttaat cttaatttag atgaaaagac aataaatcaa 25620ccacttcgtg agttgaaaat cgattcactt gatatgttta gtattgttgt tagtctagaa 25680aatgaatttg ggattagttt tgatgatgaa aagttaatga atctaaaaaa tcttgctgac 25740ttggttttag aagttaaaaa ccttttagca aaaaaagggg tatagatttg atagcgttct 25800tttaatgaca agaagacaaa accagatggt aaaactcacc acttggttaa aaaaaattgg 25860ctgaggtgag actattaccc aacgaatttt ttgtttttat atctattgca tcttgtttgg 25920aagtttgctg ttatttttgc caattgcact ccaagataac taccaaaaag tggttagtta 25980tggaattgat tgacagggaa aaagatttga acagaaaact gattacaact ttttagatgc 26040attattttta tcaaccagtg cttttagtga tacaggactt tctactgttg ttgtatcaaa 26100aacatacagt atctttggcc agatagtttt agcagtatta ctccagttag gagggattgg 26160atttgttgtt attgcttttt tagcatgacg attgtttaac tttcacaaga aggaacaata 26220cagtttttat gaaaagttaa tgttgcaatc agaacgaggt ggttctaagc taggtaatac 26280tagtgagatg atcttagtat ctatcatctt tctttttatc gttgaactaa tttatggatt 26340tttatatggt attttgtttt atttcatccc aggctttgaa cctgctaact tgtttgcaga 26400tcatgcaaaa gtttcaactc aattaaaagc tttagtagtt gattcaaacc aaacaatagc 26460agcttttaat gatattaata aggcttttca agcaggtttt ttccattcct tatcagcagt 26520taataatgct gggatagatc tgataggggg tagttctttt gttccttata gaaatggact 26580tggtattatt attcagtggt taactattag ccaaattatc tttgggggaa ttggttatcc 26640ttgtttgttt gatggctttg aagccattaa aaaaaagatt aagtatggta gacacacaaa 26700acaccaattt agtctattta ccaagttgac agtaattact aatatcgttg taatcctgct 26760ttttttcacc ttacttttaa tggtggaatt tattgctagt gatagtttaa ctaacactat 26820tgttaatttt agtgatgaaa aaaagagttt aataaatacc caattgcaat cacaatctaa 26880ccaagcaatc catgcgtcag tttttggtaa taaccctaat gcaagtaggg taatgcagct 26940cttttttatg gttatttcat cccgttcagc aggttttagt gttttccctg ttgctagtga 27000gattcaaact acaaaaataa ttattgcatt ggcaatgttt attggtgcta gtccctcttc 27060tactgctggg gggattagaa caactacgct agcagtaatc tttttagctc tagttgctaa 27120gtttaaaggt caaaaggaag taaaagcatt taagcgttca atcgatcaaa ctacagtaat 27180agatgctttt ttagtactaa tcataagctt aattgcagtt ttactaacag ctgttcttct 27240acctttaagt atggaacaac cagttagttt cattgatgct ttatttgaaa caactagtgc 27300ttttggaaca gttggacttt caagtggagc tactgttaac attgctttag atccaaatag 27360aaataccttt aatttccttg ctttatgtct attaatggtt atgggacagg ttggtgtgtc 27420cagttctgtg ctaacttttg ttagaaaaca tcccaaagca aatagttatt catatcctaa 27480ggaagctgtt aaaattggct agacacaaag ttgaccaagt tgctaataat ttttaatctt 27540acatgccacg taagcatcta attgctaatc aaactaataa aaaacaacaa acaagtgcaa 27600aacaacttca aaaactagca aaaagaatag cttcagctgt taaaaaaggt ggaactaata 27660tccagtcaaa tccacatcta aaagttgcag ttgatcttgc tttagctaag ggtctaagca 27720tggattcaat taaaagaaat atccatggta gtgaaaaaga tacaactaaa attagcgagt 27780tttgttatga gatttttgga ccaaatggtg ttggaattat tgtgtttgga ctaactgata 27840atcctaaccg tttactcagt agtttaaacg gttatttagc taaactaaaa ggacaattag 27900ccaagccaaa tagcgtcaag attaattttc aagaagaagg gattatcttt gttaataaaa 27960ataactattt gaaagatgat ctaattgaat tattaatttt ggacaatatt aacttaattg 28020atgttgatta tgatgaagag tgttttgaaa ttagcttgca ttcaaatagt tattttcatg 28080caaaggagct gttgaaaaaa aacaattttt caatagtaga tagtgaaatt aaattggtac 28140ctcttttaac tgttgattta gatagaaatc agcaaacttt attatcacgt tttctcaatg 28200cttgtgagga agatgatgac attcagtttg ttgttcataa tgccaaccca tgggaagagt 28260agatgacttt gcttttagta atcctatctt tggagctttt tagtgcaaaa gaagattaaa 28320aaacgtttaa aaaaagagaa tcttttaaga atcttttcaa agactttagc attcttgttt 28380ttagttttat ttataagttt ttttgttttt cttttaacag aagcaacaaa aattggacct 28440gattttgcaa agtccttgtt taatcttgaa tttaatttag gtaataaaca ggcaggaatt 28500tgattcccct tattggtaag ttttattgta tcaataggag ctttaattat tgctagttat 28560ataggggtta gaacttcatt tttccttgtt tatcgatgca aaccaaaaat aagaaaaaaa 28620ctttcactta ttattgatat cctttcagga ataccatctg taatttttgg attatttgca 28680tcacaaatat taagcatttt ctttcgggat atcttgaaat taccgccgct ttcactttta 28740aatgtgatag ctatgctttc ttttatgatc attcctattg ttatttcatt aacaacaaat 28800acattaactt atgtaaataa cgatctaatt agtgttgttg tttccttagg ggaaaataaa 28860acaagtgcga tctacaaaat tattaaaaaa gaaattaaac cacaattaac agttattttg 28920accttagcct ttgcgagagc aattagtgaa acaatggctg ttaactttgt tttgcagagt 28980gttaactatc aagaggtaat taacaacaat cgttttttta cttctgattt aaaaacactg 29040ggatcagtta tttccacttt tattttttca gaaaatggag atgaacagat taatggtgtt 29100ttatatatct ttggaatcat aattttgata ttagtttcat tgttaaattt ctttgccatt 29160tgatcagcta atccaaaaac actggaacgc tatccctttt taaaaaagat tagtaatttt 29220atttatcaag ttgtgtgatt cattcccaat aatattagtg cactttttgt tgatttaaca 29280tcaacaagac aaagtgttaa aaaaataaaa gtaaacaaca tcaatgaacg ttcacttttt 29340tttaaagaaa ggcttcaaag tgttgtttga ataaaactta attatttttt aaaaatattc 29400caggaattaa tttgtacttt tttagctttt ggatttgtgt tagcaatttt gctgtttgta 29460tttattaatg gaagtgttgc tattaataat aatggttcta ctgttttttc atttgaagct 29520gattcaactg gcagagcact agtaaatact ctagtaatta ttttgattac tatcaccatt 29580acttttccac tagcactttt aattgcaatt tgacttaacg agtacaataa ttcaaaagtg 29640gttaaaaatg tttttaactt tgtaattgat tcactaagtt caatgccatc tattatttat 29700ggattatttg gactttcttt ctttttaaga gtcttgcagt taagtgctgg aggagctaat 29760ggtactagtt taatagcagg cattctaact attagtgttg ttatattact cttccttata 29820agaacttgtc aacaagcact aaataatgtc agttgggatt taagaattag tgcttttgct 29880ttaggtataa gtaaacgtga agttattttc aaaatagttt tacctagtgc tttgaaagga 29940ttaatagttg cattaatttt gtcaatcaac agaattattg ctgaaactgc acccttcttt 30000atcacttcag ggttatcatc tagtaattta tttcatttgt cattgccagg tcaaacacta 30060acaacaagga tatatggaca gttattttct attaatagca atgcaataag tgttatgtta 30120gaaacatcat tggtctctgt tgttttctta attcttttaa tctttttcag ttcttattta 30180atcccgagtt tatttttgtt aaataaacaa aaatggctag taattaaaag taaatttcag 30240tcctttaaat tatggaaaag aacataaaag cactttgaaa aaattttcaa ttgaagcttg 30300aaaaaattaa gcattaccga aagctttatg aacaacaaat caaagaatat aaaaagaaaa 30360ttactggttt aaataatgaa acagatgcaa atgaaatctc ccgtattaag aatgaaattg 30420aaattttaaa ccgtctaata aagattaaaa acaccaaaga taatgtcatt aaaaaggatt 30480ttgatgaaaa aaatgtattt gaaattcgaa atttcaactt ctgatataac aaaaacaaac 30540aagtattatt tgatatcaat cttgacatta aacgcaataa aataactgct ttaataggta 30600aatcaggatg cggtaaatcc acctttatta ggtgcttaaa taaattaaat gatttaaatg 30660aaaacacacg ttgaacaggt gacatatatt ttcttggtaa gaatatcaat tcaggaatta 30720ttaatgattt aacattgcgc actagtgttg gcatggtttt tcaaaaatta actcctttta 30780atttttctat ttttgaaaac attgcttatg gcataagagc acatggtatt cacaataaaa 30840atgctatcaa tgaaatagta agacaggcat tgatatcagc agcattgtga gatgaagtga 30900aagataattt acataggaat gcaaacaccc tttctggtgg acaacaacaa cgcttgtgta 30960ttgcgcgtgc tattgcttta caaccagatg ttcttttgat ggatgaacct accagtgctt 31020tagactcaat tgccacaaac tctattgaac ttctaattca acaactaaaa gaaaaattca 31080caattgttat tgttactcac tctatggctc aaacaattag aataactgat gaaacgattt 31140tttttgctga tggaagagta attgaacaag gcactacaaa acagatattt acaaagccta 31200agcaaaaagc aacaaatagt tatataagtg ggaaaaatta g 31241 14 4750 DNA M.genitalium 14 aacacctaac aaagtttgtc caacgcttgg ttaaataact atggatgaaaatgaaactca 60 attcaacaag ttaaaccaag ttaaaaacaa gctgaaaatt ggtgtttttgggattggagg 120 tgctggtaat aacattgttg atgcatcact ttatcactat cctaatttagcaagtgaaaa 180 catccacttt tatgctataa attcagattt acaacacctt gcatttaaaacgaatgttaa 240 aaataaactc ttaattcaag accatactaa caagggcttt ggagcggggggtgatccagc 300 taaaggagct agtttagcaa taagctttca agaacagttt aatacacttacagatgggta 360 tgatttttgt atcttagttg ctggatttgg taagggtact ggtacaggtgctaccccagt 420 ttttagcaag atcttaaaaa ctaagaagat cttaaatgtt gctattgttacctatccatc 480 tttaaacgag ggattaacag tgagaaacaa agccactaag gggcttgaaattctcaacaa 540 agcaactgat agttacatgc tattttgtaa tgaaaaatgt acaaatggtatctaccaact 600 agcaaacaca gagatagtca gtgccattaa aaacctaata gaactaattactattccttt 660 gcagcaaaac attgattttg aagatgtacg tgcctttttt caaaccaaaaaaactaacca 720 agatcaacag ctttttactg ttactcaccc ctttagtttt agctttgatagtaaagatag 780 tatagaacag tttgctaaac agtttaagaa ctttgaaaaa gttagttattttgaccactc 840 tatagtagga gctaaaaaag tgttattgaa agctaacatt aaccaaaagatagtcaagct 900 taacttcaag cagatccaag atattatctg aactaaaatt gacaactaccaacttgagat 960 taggttaggg gttgattttg tgacaaccat ccctaatatc caaatttttatcctcagtga 1020 acacaaaaat ccagtttcgc ttcccattga taataaatca actgaaaacaaccaaaataa 1080 gttgaaactt ttagatgagc tgaaagaact tggcatgaaa tatgttaagcaccaaaacca 1140 aatctactaa tgaaaaatat gtatctgaaa atgattctaa ttaactaataatgggctttt 1200 taagcaagtt aattgccaaa ctaaaaccaa aaaaatcagt tgctaaacagcttaaagaag 1260 aagttgaaaa acaaagcctt tttcaaacca ataataaaac ttactatcagggtttgaaaa 1320 aatctgctac aactttcgct aaaactatta atgaactgtc aaaacgatatgttaatgttg 1380 acgaacagtt taaagaaaat ctatttgaag ggctagtttt gcttgatgttggttatcatg 1440 ctgcaaacaa aatttgtgat gctattattg aacagatcaa gctaaacagaattacagatt 1500 ttcagctcat taaagagcta attattgacc aaattattgt ttattacatccaagataaac 1560 tctttgatac tgatttaata gttaaaccta actttacaaa tgtttatctctttgttggtg 1620 ttaatggagt tggtaaaaca actactttag ctaagatagc ggattttttcataaaacaaa 1680 ataaacgtgt tctacttgtt gcaggtgata cttttagagc aggagccattgaacaactta 1740 atcagtgagc aaagctgtta aactgtgaca ttgtacttcc aaaccctaaagaacaaactc 1800 cagctgttat ctttcgtggc gtaaagaaag ggattgatga taaatatgactttgttttat 1860 gtgatacatc aggaagattg caaaacaagc ttaacttaat gaatgaattgcaaaaaattt 1920 atcaaattat tcaaaaggta agtggaagtg aacctagtga aacacttttagttttagatg 1980 gtacagtagg tcaaacagga ctatcacaag caaaggtatt taatgaattttccaaactaa 2040 cagggattgt tttaactaaa atggatggtt ctgctaaggg tggaattattttagctatta 2100 aagatatgtt taacctgcct gttaaactga taggttttgg tgaaaaaactagtgatttag 2160 ctatctttga tctggaaaaa tatgttttag gtttacttaa taacttaaacttagataata 2220 aagaaaatta gtagcaataa cagagctaat aaagttttaa aaaataattatatggaaaaa 2280 acatcaaata caagtaagcc actttctcgt agtgaaatca ataaaataattgcagttgct 2340 actggtataa aagaaaaaaa aattaaggaa atctttaaat accttaacacattgttacta 2400 aatgaattgg taagtagaag tgtttgtata ttacctgaaa atttaggtaaattaaggatt 2460 actattagaa atgcacgtta tcagaaggat atgcaaacag gtgagattagacatatccca 2520 ccaaaaccat tagtgcgcta cagtccaagc aaaacgatca aagaaactgcagctaaagtg 2580 cgttgaaagt acgcagacta atcaaaccaa aaaaacccaa atcggtcaaaaactaacata 2640 gatgaaaaaa agaaataagg gtttagtaga acaaacaact actgaaaaaaataatttttc 2700 acgtaaaact gcttgaaaag tcttttgatg agtcatcatt ttagctgttgttattggtgt 2760 tttagcttat attttcagtc caagagctgc tactgcagta gttgaaagctgaaaattaaa 2820 tggaggtagt aacagcactt taacagcaaa agtaagcggt tttagtaatgaactgacatt 2880 taaacaaata aatggttcaa cttatgttac tgataccatt ctccaagtttccattacctt 2940 tgatggttta aatagtccat taactgttac tgctcacaaa actgttaatagtaatggcaa 3000 tgttatcttt aatattgcta acttatcaat taaccaaagt aatggtcagattaccgttaa 3060 tagtaatgga accatgatga atggtggttc tagtaataac acaaagagtattgcaggttt 3120 tgaaaccctt ggtactttca ttgctcctga tactagagct agagatgtattaaatggttt 3180 gtttggcttg ctaccaatta ttatctttgt agttttcttt ttactcttttgaagaagtgc 3240 taggggtata tctgcagggg gcagagaaga agataatatt ttttctattggcaaaaccca 3300 agctaagttg gctaagtcaa ctgtgaaatt taccaatatt gctggacttcaagaggaaaa 3360 gcatgagttg cttgagatag ttgattattt aaaaaatcca ttgaaatatgcccagatggg 3420 agcaagatcc ccacgtgggg taattttata cggtccacct gggacaggtaaaacattatt 3480 agctaaagca gtagctggtg aagctggtgt tcctttcttt caatcaacgggttctggatt 3540 tgaagatatg cttgttggtg ttggtgctaa acgagttaga gatcttttcaataaagctaa 3600 aaaggctgct ccttgtatta tttttattga tgaaattgat tcagttggttctaaacgggg 3660 tagagttgaa ctctcttctt attctgttgt tgagcaaacc ttaaaccaattgttagctga 3720 aatggatgga tttacaagca gaacaggtgt tgttgtaatg gcagctacaaataggttaga 3780 tgtattagat gatgcattat taagacctgg aagatttgat agacatattcaaatcaatct 3840 ccctgatatt aaagaaaggg aagggatttt aaaagttcat gctgaaaataaaaatctctc 3900 ttctaagata agtcttttag atgttgctaa gagaactcct gggttttcaggtgctcaatt 3960 agaaaatgtt atcaatgaag ctacattgtt agcagttaga gacaaccgtaccacaattaa 4020 cattaatgac attgatgaag caattgatag agtaatagct ggtcctgctaaaaagtcacg 4080 tgtaattagt gatgaagata gaaaactagt tgcttatcat gaggctggtcatgccttggt 4140 tggtttacat gtccacagta atgatgaagt acaaaagatt accattattcctcgtggtca 4200 agcagggggt tacacacttt caacacctaa gagtggtgat cttaacctaaaaagaaaatc 4260 tgatttactt gcaatgatag caactgctat gggcggtaga gctgctgaagaggaaatcta 4320 tggtaattta gaaattacta ctggcgcttc tagcgatttt tataaagcaactaatattgc 4380 aagagcaatg gtaacccagc ttgggatgtc taaattaggt caagtgcaatatgtaccaag 4440 tcaagggaca ctcccttcta atgtaaaact ttattcagaa caaactgctaaagatattga 4500 caatgagatt aatttcatta ttgaagaaca gtataagaaa gcaaaaacaatcattaagag 4560 taaccgtaag gaactagaat tgcttgtaga agcactttta attgctgaaactattttgaa 4620 aagtgatatt gacttcatcc ataaaaacac taaactacca ccagaaatcttattgcaaaa 4680 gcaagaacaa caagcaaagc aaaaactaaa taaatctgaa gtaaaaccagaaagtgaaac 4740 aaacagttag 4750 15 13894 DNA M. genitalium 15 gcaagaattataattaacac tctaaggatg caagtgataa atggctgctg gtaaaaggga 60 ttattatgaagttctaggga tatctaaaaa cgctagttct caagacataa aaagagcttt 120 tagaaagcttgcaatgcaat atcaccccga tcgtcataaa gcagaaaatg aaactactca 180 aaaacaaaatgaggaaaagt ttaaagaggt taatgaagca tatgaagttc taagtgatga 240 agaaaaacgtaagctttatg accagtttgg tcatgaaggg ttaaatgctt ctggttttca 300 tgaagcagggtttaatcctt ttgacatctt taatagtgtt tttggtgagg gattttcctt 360 tggaatggatggtgattcac catttgattt catttttaat cgttctaaaa aacgtcaaca 420 acaaattgttgttccctata accttgatat tgctttagta attgaaatta acttttttga 480 aatgactaatggttgcaaca aaaccatcaa atatgaaaga aaagtttcat gtcatagttg 540 taatggttttggcgctgaag gcggggaaag tggattggat ctttgtaagg attgtaatgg 600 caatggttttgttattaaaa accaacgttc tatctttgga accattcaat cccaagtctt 660 gtgttcaacttgcaatggac aaggaaaaca aattaaagtt aagtgcaaaa cttgtcgttc 720 taacaaatacactgttacca atcaaattaa agagattaat attccagcag gaatgtatag 780 tggtgaagctttagttgatg aaagtggtgg taatgaattt aaaggtcact atggaaaatt 840 aatcattcaagtgaatgtat tggcaagtaa gattttcaaa cgtagtgata ataatgttat 900 tgccaatgttttagtagatc caatggttgc tatagttggt ggggtaattg aactacctac 960 tcttgaagggattaaagaat ttaatattag accaggcact aagagtggcg aacagattgt 1020 tattcctaacggtgggatta aattctcaaa gagttttaaa agaaaagctg gggacttaat 1080 cattattattagttatgcac gtccttgtga atacactaac ttagaattga aaaaattacg 1140 tgagtttatcaaacctaatc aagaggttaa acaatattta aatactttaa aaaatgaata 1200 caaaacttaattttattaaa acattattta ataataaata attaaaaatc atgttcaaag 1260 caatgttatcaagcatcgtt atgcgcacga tgcaaaaaaa aattaacgct caaacgatca 1320 ctgagaaagatgtagagtta gttctaaaag agattagaat tgcattgctt gatgctgatg 1380 ttaacctgcttgttgttaaa aatttcatca aagcaattag agataaaaca gtaggacaaa 1440 ccattgaacctggtcaagat ttgcaaaagt ctctattaaa aacaatcaaa acagaactaa 1500 ttaatatcttaagccaaccc aaccaagaac taaatgaaaa aagaccttta aaaataatga 1560 tggttggtttacaaggatca ggtaaaacaa caacttgtgg caaactagct tattgacttg 1620 aaaagaaatacaagcaaaaa acaatgttag taggcttgga catctacaga cccgctgcca 1680 ttgaacaacttgaaacgctt tcacaacaaa ctaacagcgt attttttgca caaggcactc 1740 aaccagttgctaaaacaaca aaagcagcac tcagtgcttt taaaactgca aaatgtcaaa 1800 caatcatttgtgataccgct ggtagattac aaacaaatga aacattaatg gatgaattgg 1860 taagtgttaaaaatgaatta aatcctgatg aaattatcat ggtagtagat ggattaagcg 1920 gtcaggaaattatcaatgtt gctcaaacgt tccacaaacg tttaaaacta actggattta 1980 ttatcagtaaattagacagt gatgctagag caggagctgc actttcatta gcttcacttt 2040 tacaagtacccattaaatta attggtgttt ctgaaaaatt agatggattg gaacaatttc 2100 atcctgaaaggatagccaat cggatcttag gtttgggtga tgtaatgagt ttagttgaaa 2160 aagctgaacaagtttttgat aaaaaagatt taactaaaac catcagcaag atgtttttgg 2220 gaaaaatggatttagaagat cttttgatct acatgcaaca aatgcacaaa atgggaagtg 2280 tcagttcactgataaaaatg ttgcctgcta acttttctgt atcagaagaa aatgctgaat 2340 taattgaaaacaaaattgaa ctatgaaagg ttttaattaa ctctatgact agagaagaaa 2400 ggagacatcccaaattaatt aatcgtgatc ctaatagaaa acagcgcatc ataaaaggtt 2460 cagggagaaaaatggatgag ttaaacaaac tgatgaagga atgaaataag atgcaactaa 2520 aagcaacagaaatgggtaaa ctattaaaaa caggtagtaa cccgtttggt ggatttggac 2580 aattcttttaacaatcaaaa aactaagcat ctagattctt tttaaaaagc catggaaaaa 2640 aaactgccttttagctttaa aaagaaggaa aagctaactg cttatgatga tgcttcaatt 2700 catgagttacataaacagct caaacttaga acagaagcca agaaaagtaa agataaggaa 2760 agaactaaagaaaaagaaaa gcatgaaagt ttagcaaagg aaaagaaacc caagcttcct 2820 tttaaaaaacgaattgttaa tttatgattt ggagttgata aagagatcaa caaaattgtt 2880 tgagtaaaaggtagacaact tatcataatt tttcttttaa ttttgctagt tagtggactg 2940 atggtaggaatcttttttgg tatcaatcaa ttgttaatta cgttgggaat atttaaaaat 3000 taattaaacattaaccgtca acaacaagaa actttataga gcaatggcaa tatttaactt 3060 ccttaagttaatttcaccca aaaacagaat tctcagtaag gcaaatagga ttgccagtga 3120 ggttgagagttataaaaact actaccgtaa cttaactgat caacagttat ttgaagagtc 3180 aaataaactagttgatcttg tcactaagca aaattacacc attctagatg tttgtgttgc 3240 tgcacttgctttaattagag aagtggttta ccgtgagact ggtgaatttg catatagggt 3300 gcagatcataggagctttta ttgttttaag tggtgatttt gctgagatga tgactggtga 3360 aggtaagaccttaaccattg ttttagcagc atacgtttct gcacttgaaa agcgtggtgt 3420 gcatgttgttactgttaatg aatatctagc tcaaagggat gctaataatg caatgaagat 3480 cttaaaacgggttgggatga gtgtcggttg taactttgct aatctctccc ctcagctaaa 3540 acaagctgcatttaattgcg atgttaccta caccactaac agtgaactgg ggtttgatta 3600 tcttagagataacatggtcc acagttatca agataagaag atcagagagt tgcactttgc 3660 aatagttgatgaaggtgatt cagttttaat tgatgaggcg cgaacgcctt taattatttc 3720 aggtcctagtaaaaatgagt ttgggttata tgttgcagtt gatcgatttg ttaaatcatt 3780 aactgaacaggagtttaaga ttgaccctga atcacgtgct gcttctttaa ctgaacttgg 3840 gattaaaaaagcagagcaaa catttaaaaa agaaaacctt tttgctttgg aaaacagtga 3900 tctttttcacaagatcatga atggtttgac tgctgtgaaa gtttttgaac agggcaaaga 3960 gtacattgttcgtgatggca aggttttaat tgttgatcac tttacaggta ggatattgga 4020 agggagaagttacagtaatg gcttacaaca agctgtacaa gccaaagaat atgttgagat 4080 agaacctgaaaatgtgatag tagctaccat tacctaccaa tccttcttta ggctatacaa 4140 ccgcttagcagcagtatcag gtactgcttt aactgaatca gaggagtttc tcaagattta 4200 taacatggttgtagtaccag tgccaactaa ccgtcctaac atcagaaaag accgttctga 4260 tagtgtatttggtaccccac aaattaagtg aatggcagtt gttaaagaga taaaaaagat 4320 ccatgaaacttctcgaccta ttctgattgg aactgctaac atagatgatt ctgaactctt 4380 acataatctgttactagaag ctaatattcc ccatgaggtt ttaaatgcta aaaaccattc 4440 aagagaagcggagatagtaa ctaaagcagg acagaagaat gcagttacta tttcaactaa 4500 catggctggaagaggaactg atatccgttt aggtgaaggg gttgctgaaa tgggtggtct 4560 ttatgtattgggaactgaaa gaaatgagtc aagaaggatt gataaccaac taagagggag 4620 agctgctagacaaggtgata aaggggaaac taagttcttt atctcactag gtgattcatt 4680 gtttaaacgttttgctcatg acaagattga aagagcgatt agcaaattag gtaatgaaac 4740 atttgacagtgccttctttt ccaaaatgtt aagtagaacc caaaaacggg tggaagcaat 4800 taactttgacactagaaaaa acctgattga ttatgaccat gttcttgcaa gtcaaaggga 4860 attgatttacaaacaacgtg ataagttttt attagcaaac gatttaagtg aaatgatcga 4920 caaaatgctagaaaagtttg tacaacagtt ttgtgatcaa tatagaaacc aaaagaacca 4980 aaacttaattaatcacattg cactagcaga agctttaaat cttgagatga acatgcaaaa 5040 caccattaatccaaaggtgt ttgaaaacat gacttttgat gttgctgttg ataaaacccg 5100 taacttagtagctaaaaaga ttagtgataa agttaatgtt ttgaccaaac caattgcttt 5160 aaacaggtttcgtgacatta tcataacttc gatggataaa cattgaactg aacacttgga 5220 tagtgtttttaagttaagag aaggggttgt acttcgttct atggaacata cgagtccttt 5280 aaatgtttacattaaagaaa cagatatcct ttttaaaaca atgttgcaaa agattgctca 5340 agatgtcattgtgcaaattg ctaacctcac aactccagat gaatttgatc atagcttaat 5400 gcaagccaatgctttaaaga aactagcagc aattaaagca gatgaaaaat caaaccaaga 5460 gtaagcttaaaattaagata aataattttc caattttgtt ttcaatggaa caaaaaaaca 5520 ttagaaatttttctattatt gcccatattg atcatggtaa atctacctta tcagaccgct 5580 tgttagaacatagtttaggc tttgaaaaaa gactattaca agcgcaaatg cttgatacta 5640 tggagattgaaagagaaagg ggtattacca ttaaattaaa tgctgttgaa ttgaaaatta 5700 atgttgataacaacaactat ctttttcatt taattgacac ccctgggcat gttgatttta 5760 cttatgaagtgtctcgttct ttagcagctt gtgagggagt tttattgtta gtagatgcaa 5820 cccaaggaattcaagcacaa acgatttcca atgcttatct tgcgttggaa aataacctgg 5880 aaattatcccagttattaac aagatagata tggataatgc tgatattgaa acaacaaaag 5940 attcactccataacttatta ggagttgaaa agaacagtat ctgtttagta tctgcaaaag 6000 ctaacttagggattgatcag ttaattcaaa caattatagc taagatcccc ccaccaaaag 6060 gagaaattaatagaccttta aaagcattac tctttgatag ttactatgat ccttacaagg 6120 gggttgtttgttttattagg gtatttgatg gttgtttaaa ggttaatgat aaggttcgtt 6180 ttattaaaagtaattctgtt taccaaattg tggaactagg ggttaaaacc ccattttttg 6240 aaaaaagagatcaattgcaa gcaggagatg ttggttggtt ttcagcaggg ataaaaaaac 6300 ttcgtgatgttggggttggt gatactattg ttagttttga tgatcaattt acaaaacccc 6360 tagcaggttataaaaagatc ttacccatga tctattgtgg tttatatcca gttgataaca 6420 gtgattatcaaaacctcaag ttagcgatgg aaaagatcat aatcagtgat gcagcattgg 6480 aatatgaatatgaaacatcc caagcgttag gttttggggt taggtgtggt tttctaggtc 6540 ttttacatatggatgttatt aaagaaagat tggaaagaga atacaaccta aaactcatct 6600 cagctcccccttcagttgta tataaggtgt tgttaacaaa tggtaaagag attagtattg 6660 acaatccctctttgttacca gaacgctcca agattaaagc aatcagtgaa ccatttgtaa 6720 aagtctttattgatttacct gatcaatatt tgggcagtgt tattgattta tgccaaaact 6780 tcaggggtcaatatgaaagt ttaaatgaga ttgatatcaa cagaaaaaga atctgttatc 6840 tgatgcctttaggggaaatt atctacagtt tttttgataa gttaaagtcg attagtaagg 6900 gttatgcatcgttaaactat gagttttata actaccaaca tagtcaactg gaaaaagttg 6960 agatcatgttaaacaaacaa aagattgatg cattatcttt tatcagtcat aaagactttg 7020 cttttaagcgggcaaaaaag ttttgcacta agctcaaaga attgattccc aagcatctgt 7080 ttgagatccctatccaagca acaataggga gtaaagtaat agcaagagag acaatcaaag 7140 cagttagaaaggatgtaata gctaaacttt atggagggga tgttagtaga aaaaagaagt 7200 tattagagaagcaaaaagag ggtaaaaaac gcttgaaagc agttgggagt gttcaattac 7260 cccaagagctatttagtcat ttgctgaaag atgaagatta acattattaa gaaataaacc 7320 aattagtgatctataaaaac aatgcaaact gtttcttcac ccaaacaaaa acttaacttt 7380 ggtcaaaggttactaactct attacagaac cgtgacttta tggtgtcgct ggttttaaca 7440 gtggtacttttaatcttgtt tagggtgtta gcaattatcc ccttaccagg gattaggatt 7500 aatgagagtgtcttggatag aaattccaat gacttttttt cactttttaa cttacttggg 7560 ggtgggggattaaaccagct atcgttgttt gcagttggga tcagtcctta tatctcagcc 7620 caaatcatcatgcaactgct ttcaactgat ctaattcctc cactttcaaa gctagttaac 7680 agtggggaagtggggcgaag aaagattgag atgatcacaa gaattatcac cttacccttt 7740 gctttagtgcaagcatttgc tgtgatccaa attgctacta atgcaggcac tggttcaagt 7800 ccgattagtttagctaatag tggcagtgag tttattgctt tttatattat tgctatgact 7860 gcagggacttatatggcagt gtttttgggt gatactatct ccaaaaaagg ggttggtaat 7920 gggattactttgttaattct ctcagggatt ttatcccaac tcccccaggg ctttattgct 7980 gcttacaatgttttgagtgg gatagtaatt actctaaccc cacagttaac tgcagcaatt 8040 agcttctttatctatttctt agcattctta gttttactgt ttgccactac ctttatcacc 8100 caagcgaccagaaagattcc catccaacaa tcaggacaag ggttggttag tgaagtcaaa 8160 accttaccttatttgcctat taaggtgaat gctgctgggg tgatccctgt catctttgca 8220 tccagtattatgtctatccc tgtgaccatt gcccagtttc aaccccaaac tgagtcacgg 8280 tggtttgtggaggattacct atcactttca acacccgtag ggatcttttt atatgcagtt 8340 ttggttatccttttttcctt tttttacagt tacatccaga ttaacccaga acggttagct 8400 aagaactttgaaaaatctgg cagatttatc ccagggattc gaccgggcaa tgatacagag 8460 aaacacattgcgcgggtgtt aataaggatt aactttatag gtgctccttt tttaactgtt 8520 attgctattatcccttacat tgtttcttat ttcattaggt tacctaactc cttgagttta 8580 ggggggacggggattattat tattgttact gctgtagttg aatttatcag tgcactgcgt 8640 tcagctgctactgctactaa ctaccaacaa ctaaggagaa acttagcaat tgaagtgcaa 8700 caaacagctaaacaagatag tctagagcag cttcaaaaag aagcaccagg gattggtaac 8760 ctatggtagaatacctctcc caagaaccca ttagttagaa tttgttaata tgtgtgaaaa 8820 atcacaaacaattaaagagc ttttaaacgc cattagaacc ttagttgtca agaacaataa 8880 agctaaggttagtatgattg aaaaggaact gttagctttt gttagtgaac ttgacaaaaa 8940 gttcaaacaacaactcaaca acttcaatga actacaacaa aagatcccac tactccaaaa 9000 agctaacgaagagtttgctt taaagtttga aaggatgcaa cgcgaagcac aaaaccagat 9060 ccaagccaaactagatgagt tgaatcttaa aaataaaaag gagttagaac aagccaagaa 9120 atatgcgattgccaaaaccc ttgaccaacc cttaaacatc atcgatcagt ttgaaatcgc 9180 gctttcatatgcccaaaaag accctcaagt aaaaaactat accactggtt ttaccatggt 9240 acttgatgctttttcaaggt gattggaagc aaatggggtt accaagatta agattgaacc 9300 agggatggaatttgatgaaa agattatgtc tgcattggaa ctagttgatt ctaaccttgc 9360 taaaaacaaggtagtaagag tctcaaaatc tggctataaa ctctatgaca aagtgatccg 9420 ctttgcatcagtatttgtca gcaaaggtaa taaaaaatca taaaaactta agagtttaaa 9480 cttatctttaaccgatccac tccatgaaat taagaaaaac caagtttttt tcacaactta 9540 aacaccaggttttaactgca aaccaaaaac catttttatt ctataaactg acaatgattg 9600 ggtttgttggctttattatc ttactgcaag ttttcatatt aagaaatgcg ttaaatggtg 9660 agatggataacaccatggta gcaaatagtg gttttattaa tatctatgtg attagaaaca 9720 aaggggtagggtttagctta ttacaaaacc aaactggctt agtttacttt ctccagggat 9780 tattatcagtaattgcgtta gtttttcttg tttttatggt gaaatatagt tacatctttt 9840 gaattacaactttagcattt ggttcacttg gaaacttctt tgatcgttta acttcagcta 9900 atgattcagtgttagattac tttatctttc agaatggtag ttcagtattt aactttgctg 9960 attgttgtattacctttggt tttataggtt tattcttttg ttttttaatc cagatgttca 10020 aagagtttaaacattccaaa aaccagtaat ataattactg agtaattgtt attgatctaa 10080 aaaaaaagtatgagtgcaga caatggttta attattggca ttgaccttgg aactaccaat 10140 tcttgtgtttctgtaatgga aggtgggaga cctgttgtat tagaaaatcc tgaaggtaaa 10200 agaacaacaccttccattgt ttcctataaa aacaatgaaa ttatagtagg tgatgctgct 10260 aaaagacagatggttacaaa cccaaatacc attgtctcca tcaagaggtt gatgggtacc 10320 tcaaataaagtaaaagtcca aaatgctgat ggtacaacta aggaattaag tcctgaacaa 10380 gtttcagcgcaaatccttag ttatcttaag gactttgctg aaaaaaagat tggtaaaaag 10440 atttcaagagcagttattac tgttcctgca tactttaatg atgcggaaag aaacgctact 10500 aaaaccgcaggtaagattgc tggtttaaat gttgaaagga tcattaacga accaactgct 10560 gctgctttagcttatgggat tgataaagca tcaagagaga tgaaagtctt ggtttatgac 10620 ttgggtggtggaacttttga tgtatcttta cttgacattg cagaaggtac ttttgaagta 10680 cttgcaactgctggggacaa ccgtttggga ggtgatgatt gggataacaa gatcattgaa 10740 tatatctcagcctacattgc caaagaacac cagggtttaa acttatcaaa agataagatg 10800 gcaatgcaacggcttaaaga agcagctgaa cgtgctaaga ttgaactttc cgctcaactt 10860 gaaacgattatttctctacc atttttaact gttacccaaa aaggtcctgt taacgttgag 10920 ttaaaactaacccgtgctaa gtttgaggag ttaacaaaac cactacttga aagaacaaga 10980 aaccctatttcagatgttat caaggaagct aagattaaac ctgaagagat taatgaaatt 11040 cttttagttggtggttctac aaggatgcct gcagttcaaa agctagttga atcaatggta 11100 ccaggtaaaaaaccaaaccg ttctattaat cctgatgaag ttgttgctat tggcgctgct 11160 attcaaggtggggttttacg tggtgatgtt aaggatgttt tacttttaga tgtaactcca 11220 ttaaccctttctattgaaac tttaggtggt gtggctactc ctttaattaa gagaaataca 11280 actatcccagtaagtaaaag tcaaatcttt tcaactgctc aagataacca agaatcagtt 11340 gatgtggttgtatgtcaagg ggaaagacca atgtctagag ataataagtc attaggaaga 11400 tttaacttaggtggtattca accagcacct aaaggtaaac cccaaattga gattaccttt 11460 agtttggatgccaatgggat cttaaatgtt aaagctaagg atttaaccac gcaaaaggaa 11520 aacagtattaccattagtga caacggtaat ctttctgagg aggagatcca aaagatgatc 11580 cgtgatgctgaagctaacaa ggaacgggat aacatcatcc gtgaacgtat tgaattacgt 11640 aatgaaggggaaggtattgt taataccatc aaagagatat tagcaagtcc tgatgctaag 11700 aatttccctaaagaagaaaa agagaagtta gaaaagctaa caggtaacat tgatgctgct 11760 attaaagctaatgactatgc caaactcaaa gtggaaattg aaaactttaa gaagtgaaga 11820 gaagagatggcaaaaaaata taacccaact ggtgaacaag gtccacaagc aaaataattc 11880 ttttaaattagtttttaatt attaaaatat ttttattatg aacataacgc caattcatga 11940 caacgtcttggtttcacttg tggaatcaaa caaagaagaa gtctcaaaaa aagggattat 12000 tacctcattggcaagtaatg ataaaagcga tgctaatgct aataaaggga ttgtaattgc 12060 tcttggtgctggtcctgcat atggcaaaac agaaaaacca aaatatgctt ttggtgttgg 12120 tgatattatttactttaagg agtatagtgg tatctctttt gagaatgagg gaaacaagta 12180 caaaattattggatttgagg atgtacttgc ctttgaaaaa ccagaaagtg gtaagcaaag 12240 aaaaagataaaattaaacaa ttatggcaaa ggaattaatc tttggtaaag atgcgagaac 12300 ccgcttgttgcagggtatta ataagatagc aaatgctgtt aaagtaacag taggtcctaa 12360 aggccaaaatgttattttag agagaaaatt tgcaaaccca ttaattacta acgatggggt 12420 tacaatcgcaaaagaaatag aacttagtga tccagttgaa aatattggtg ctaaggttat 12480 ttcagttgctgcagtgtcaa ctaatgacat tgctggggat ggtacaacaa cagctaccat 12540 attagcacaagaaatgacaa accgtggtat tgaaattatc aataaaggtg ctaatcctgt 12600 taacatccgcaggggtattg aagatgcaag cttacttatt attaaagaac ttgaaaagta 12660 ctctaaaaaaattaatacta acgaagagat agaacaagtt gcagctatct cttcaggttc 12720 taaagaaattggtaaactga tcgctcaagc aatggcttta gttggtaaaa atggcgtgat 12780 aacaactgatgatgcaaaaa ccattaatac aacattagaa accactgaag gaattgaatt 12840 taaaggaacatatgcatcac cttatatggt tagtgatcaa gaaaaaatgg aagttgtttt 12900 agaacaacctaaaatcttag taagctcttt aaaaattaac acaattaaag aaattcttcc 12960 gcttttagaaggtagtgttg aaaatggtaa tccattatta attgttgcac ctgactttgc 13020 agaagaagttgttactactt tagcagttaa taaactcagg ggcaccatta atgttgttgc 13080 tgttaaatgtaatgaatatg gtgaacgtca aaaagcagct ttagaagatt tagcaattag 13140 tagtggaaccttagcatata ataccgaaat taatagtggt tttaaagatg ttactgttga 13200 taatttaggtgatgctagaa aggttcaaat agctaaagga aaaactactg ttattggtgg 13260 taaaggcaataaggataaaa tcaaaaagca tgttgaactt ctaaacggaa gattaaaaca 13320 aaccactgacaagtatgatt ctgatttaat taaagaaaga attgcttatt taagtcaagg 13380 tgttgctgttatccgtgttg gtggtgcaac tgaactcgca caaaaagaat taaaactcag 13440 aatcgaagacgctttaaatt ccaccaaagc tgcagttgaa gaagggatta tcgctggagg 13500 tggtgttggtttattaaatg cttcttgtgt tttaactaac agtaaactaa aagaacgata 13560 tgaaaatgaaactagtgttg aaaacattaa agaaatccta cttggttttg aaattgtgca 13620 aaagtctctagaagcaccag cgcgtcaaat tattcaaaac tcaggagttg acccagttaa 13680 aattctcagtgaattgaaaa atgaaaaaac tggtgttggc tttgatgctg agactaaaaa 13740 gaaggttgatatgattgcaa atggaatcat tgatcccacc aaagtaacta aaactgcact 13800 tgaaaaagctgcttctgtag ctagttcatt aattactact aatgttgctg tgtatgatgt 13860 taaagagagaaaagataact ccttttcaga ataa 13894 16 2556 DNA M. genitalium 16 cgtcaaaaattgttgcaaac aatctaatta aactttattg gtggattgga aaacatcaga 60 gatgctattccctttccccg tgtacatggc accattaact tctaaattcg ctgcttataa 120 aaaaaagattgcaaactggt taacagttta cagaattttt attgctttac ctactattat 180 ttttattgctttagataatc aactaggagt tttagctaac ttttctgttg gtgcaattag 240 cattagtttacagatcagtt tattgattgg aggatttttg tttttaactg cagttatatc 300 agattatttagatggatatt tagcaagaaa atggctagca gtttctaact ttggtaaatt 360 atgagaccccattgctgata aagtgattat caatggtgtt cttattgcac tagcgattaa 420 tggatattttcactttagct tattaattgt ttttatagtc cgtgatcttg tgttggatgg 480 aatgcggatttatgcttatg agaaaaaggt ggttattgct gctaactgac ttggaaaatg 540 aaaaactatcatgcagatgg ttggtattgt ttttagttgt tttgtttgga gttttaaaca 600 aagtgaaatagcttctttga atagtggact gttcttttga ttactaactc aactgccata 660 ttatttagcagcagtttttt caatttggtc tttcattgtt tataacatcc aaatatatca 720 gcaactaaaggcttataact ccaagttata aactaattgc catgttagtg ctatctgttt 780 agcacaacaaaatggataaa ctatttaaaa caagttttag attcataata aggtttttac 840 aaatcctgagtttaccagtt gtttttcctt actttttatt aagcttttta gcttgtttaa 900 ttactagtaaaaactatgaa tcactccctt ataactatcc ccctgaaatc cgattcaaaa 960 aggtgtatagattggtatca atgtgacttt acattaaggg aattaaagta gtgacagtaa 1020 atgacaagattatccctaaa aaaccagttt tagtggtagc taaccacaaa tctaaccttg 1080 atcctttagtattaattaag gcctttggca ggttgaaaaa tagtccacca ttaacctttg 1140 ttgctaagattgaactgaaa gatacagtcc tttttaaact gatgaaatta attgattgtg 1200 tttttattgatcgaaaaaac atcagacaaa ttgccaatgc attggaaacc caacaacaac 1260 taattcgccagggcactgct attgctgttt ttgctgaagg gactaggatt ttaagtaatg 1320 acattggggaatttaaacca ggagcactaa aggttgctta caatgctttt gtacctatct 1380 taccagttagtattgtgggt agcttaggaa agatggaatc aaacaaaagg ctaaaagaac 1440 atggtgttaagaaaagttca aactatgagg ttaaagtaat ctttaacaag ctaattaacc 1500 caattagttttaaccagatt gattctaata accttgctaa taacattaga agcattatta 1560 gtgatgcatacactagtgaa aaaccaagca atgattagca taatcattat tttaattgtt 1620 ggggtaattggttctctgat gatttgagag ttgttcacaa acatactaaa aaataaacca 1680 aaactaagcttaagtttaac gttgttaaat gctggaataa ttatttttgg gatgattggt 1740 acttttgttgttgtttattt ttacaaatga aatgcaactg ttaatggtat ttgaacatta 1800 agttttactctttctgtggt tttactttga ataatttaca ttgcttgcat gagtaaaaca 1860 agaattaagtttagcttaca actttcatat agcttaggag ctattgcttg ctttattgct 1920 agcataggtactatttactt ttctgttatc aggggttgaa ctacaatctt tttattgatg 1980 agtttagcagtcagtgttga tacatttcct tttctttttg gaaagcgctt tggtaaaaat 2040 cctttaattaaaatttcacc atcaaaaaca tgagaaggag ctttttttgg catcattagc 2100 accattgttgttgttgcttt actttgtgtt ttatattcaa ttcctttctt tgtagcaaag 2160 cctacttttaatcaaacaaa tggaatagcg ctcaatacac cccaaaatta tgatagccat 2220 aatcttattaccaatatttt tttaattgcc tttatctctg gaggaagtag tttttatatc 2280 tactggtgggtaagcacttt agctttaatt tttacaggat ctgtttttgc aataggcggt 2340 gatcttttttttagttatat taaacgctta attagtatca aagatttttc taaggtttta 2400 ggtaaacatgggggagtttt agatcgattt gattcaagtt cttttttaat tagtttcttc 2460 tttgtttatcatttaatagc aggaaccatt tccaaccaaa ggttgttgat ggaacctaat 2520 acttatttcagtgcaatcac tagtattcaa agctag 2556 17 2601 DNA M. genitalium 17aattgtaagt aggtataatt acagataatt tcattgataa atgttaattc ttgttaacaa 60tcctaaggct aaatatgact atcatttaat ggaatcttat tgtgctggaa tagttttaaa 120aggaagtgaa gttaaagctt taagtttagg tcaaggtagt ttaaaagaag cttatgtttt 180tgttaaaaac aatgagcttt ttttagaaca gttcactatt ccaccttata gttttgcagg 240tccattaaat cacgcttcag atagaattaa gaaactttta ttaaataaac atgaaattaa 300acaaattatc aataaaaaac aacaacaatc tttatctgta atcccaagta aagtattctt 360tagaaatggc aaaattaaag tggaaatttg attggcaaaa cctaaaaaga aatttgacaa 420acgtgaaact attaaaaaga aaacaatccg acgcgagctt gaagctgagt atcgataaat 480ttagccttag gattgttaac aagaattaac atttatcaat gaaattatct gtaattatac 540ctacttacaa ttgtgcatca tttattgaaa aagcaattaa ttcaattgtt aaaaatagac 600ctaatgattt ggaaatagaa gttttaatta ttgatgatgg atcaattgac aatactaaca 660aagttattaa gaaaattcaa gaccaaatta ataatttaac tttgcagtat ttttacaaaa 720gtaatggtaa ctggggtagt gttattaatt atgttagaaa caataaacta gcaaaagggg 780aatgagtaac agtattggat agtgatgaca ttttttcaaa aaaaacaatt tctatttttc 840aaaaatatgc ccaaaaacaa agatatgatg cgattatttt tgactactat aaatgctgaa 900aaaagttttt gtgaaaaatt cctacctatg caaggtttag aaaagaaatt aaaggtgaat 960tgaaaaaaca aacacctttt tgtattccct tagctaagtt ttttaaaaat gaggttttct 1020atcaacttcc taaactaaga gaaaatgttg gttttcaaga cgctatttat acgatgcatg 1080cattacaaat tgcaaataat gttttccatg tttctaaagc tggaggatat tactttttta 1140aaagggtagg taactctatg agtatccctt gacacagttc taggtttgat attgaagtac 1200aaatctgcaa ggatctgatt gaaaataatg cgcaagagat cgctttagtg catttacttc 1260gtttaaaatt tcgtaattta gttgatgata aaaagattaa atttacagtt aaaagagact 1320tttgttttag tggttttagt tggtatagta ggttaatttt atctctgatg tataacttct 1380gattgaaacg ttatttcaac agttctgaat aaggtgaaaa accagtgttt agcactttta 1440tacaaaagct aaatgaatag accaagttga tcaactgcat ttaatattgg tggtggattt 1500cccatccagt ggtatgggat cattgtctca attggcatta tttttgccat tttaatgttt 1560gtctttaaac tgatttattg ttacaaatta caagacaaca gtttttattt ttttatcttt 1620attgctgttt taacgatggt tttaggcgct cgcctctggt catttgtaat tggtgattcc 1680aattttgcta acaacaattt ctttgatttt cgtaacggtg gattggccat tcagggtggg 1740attttgttaa ccagtattgt cggagtaatc tatttcaact tctttttaaa tagtaagacc 1800aataaaacca aaacgattgc tgaattactg aataataaga atgaaataaa agctgtttat 1860gttgaaagaa atatctctgt tctagtgatg ttagatctga ttgctccttg tgttttaatt 1920ggtcaagcaa ttggcagatg gggtaatttt ttcaaccaag aagtttatgg gtttgcttta 1980gctggaacaa tgaatgatcc ccaagcattg gctaataccc agtggggatt tttaaagatc 2040ttaatgccta aggtttggga tgggatgtgg attgatggtc agtttcgcat tccgctcttt 2100ttaattgagt cattttttaa cactattttc tttgtgttaa tttactttgt aatggatttt 2160attaggggag ttaaaagtgg cacaattggt tttagttatt ttcttgctac tggaatcatt 2220cgtttaatct tggaaaactt tagagaccaa accttttatt ttcaaacttc aataaccact 2280agtattttgt ttattgtcgt tggtatttta ggaatttttt attgccagtt tatccatgtc 2340aaattaagaa attacttctg aacttatttc tttctttatg ccttttataa agtagctgct 2400tttttcacta cacttttttt gaataacaga aagcaaatgg cacaacagaa gtttgctttt 2460tatgaaaaat cacttcccaa taagaagcgt tctttttttg aaatgaagta ttacaatgat 2520gtaacaacac ccaaaattta tcgtttaact gatcaggaaa tgaagttatt tgataaatta 2580gaggcagtta caaccagcta g 2601 18 3706 DNA M. genitalium 18 caaaaaccaaaattattgat cttttcaata actaaagtcc atgattgatc tgcttggttt 60 ggatctggatggaacgttat tatctaaaac taaaaaaatt aacaatccat caaaattagc 120 attaactaatttaattgcta aaaaaccaag tttaaaggtg atgattttaa ctggtagatc 180 agttttttctactctaaaac acgttgaaaa gctgaacagt ttgtttaaaa aaccaattgt 240 tgattatttttgttgttatg ggggtgctaa actttatcaa attgaagcaa ataagccaca 300 agaaagatacaagttttgct tggaaaacag tgttgttgaa actaccttta gtattatcaa 360 aaaacaccgcggattatgtt tagcttactt agatagttat gtctctcctt acctttgttt 420 agctggtaacaagctccttg ggtggttcac taaatacttt tggtatagaa aaaggtgtgt 480 gttttttaaccagaaccatt taaaacaagg tattctaaag attagtgttt actttttaag 540 tgcaaaaaggtgtaaaaaag tttatgaaat cttaaaaaat acctttcaag aaaaggttaa 600 tgttttaagtttttctaata atttaattga gataactcat catgatgcta ataagggtta 660 tgcaattgaatatatggcca aaagagaaca actttcactt aatagaatag cagttattgg 720 tgattcttgaaatgattatg caatgttcaa aaaagctaaa tattcctttg caatgtcaaa 780 atccccttcccagttaaaat taattgctac caataccagt aacaaaacca accgttaccg 840 ctttagtaccttacttaatt taattagtga aacaatcatt aatcaaaaag ctgattagta 900 atgttcttttaaaaaaatag ataaaagtat atagctaaat ggaactgaaa aacattattt 960 ttgaccttgatggtaccttg ctttcaagca accaaattcc attagaacaa acagttgagt 1020 ttttaaaggatttacagaaa aaagggatta gaatcacttt tgctagtggt agaagccata 1080 ttttaattagaaacacagct acctttatta caccaaatct acctgtaatt tcttccaatg 1140 gtgcacttgtttatgatttt gctagtgaaa aaccagttca tatcaaacct attgataata 1200 aagtaatacctgcaattatg caaatgttgt tggaatttca agaaacattt tatttctata 1260 cagataaaaaggtttttgct tttacacatg agcttgattc agctaaaatt ctttcaacta 1320 gaagtcaaatagtaggaatt gatctcattg aaaataacta catagttaac aagtttgaaa 1380 aagctttggattttgatttt aagcaacata ctattacaaa gatcttactg gtaactaaaa 1440 acagagaaaaagttcctttt ctagcaaaac aactagatca aattcaagat attaactatg 1500 tgagttcaatgacatttgct cttgatatca tgcaaaaaga tgttaataag gcttatggat 1560 tgaaagtattagttgataat tataatcttg atcctgaaaa gactatggtc tttggtgatg 1620 ctgataatgatgttgaaata tttcaaagtg ttaaatggcc agttgctttg gttaatggca 1680 ctgatttagctaaaaaaaat gctaagttta ttactgaata tgacaacaat cacaacggca 1740 tttatttctttctaaaaaag tttctagcaa cttaagatta gtaaacaggt ttgctattca 1800 cgctgtttattaaaaatgtc aattattgca aaaacagttt ttataggttt aagcggtggt 1860 gttgattctgctgttagtgc tttactttta aaaaagcaat accaagaagt tattggtgtt 1920 tttatggaatgttgggatga gacacttaat aatgattttt atggtcataa gaaaataaat 1980 aataacaaatcaggttgttc atcttttcaa gacttccaac aggctaaaaa aatcgctaat 2040 tctttaggaattaagttaat aaaaaaaaac ttaattgaag cttattgaaa caaagttttt 2100 ttacctatgattcaaagttt caaaaaaggg ttaaccccaa atccagacat ctggtgtaat 2160 cgttttattaagtttggttt attgcatgat ttttgtaagc aaattaaccc taattctctt 2220 tttgcaactggtcattatgc caaaataaac atgatagaaa atcagccttt gctttctatt 2280 cctaaagataccaataaaga tcaaacttat tttttagcaa atgttaaaaa agaacaattt 2340 cagaatgttatttttccttt agcagattta aaaaaaataa cagtgagaaa tattgctaga 2400 gaaaataattgagaagttgc agataaaaaa gattcaactg gaatttgttt tattggtgaa 2460 agacatttcagtgatttttt aaaaaactat ttacctgtaa aaaaaggatt aattaaggat 2520 tgaaaaaccaaacaaactat tagtgaacat gatggtgttt ggttttatac gattggtcaa 2580 cgcagtggattaaatttagg ggggttaaaa caacgtcatt ttgttgttgc taaggatatt 2640 gaaactaatgaattatttgt ttcttgtgac aaagaagaat tattgaaaac aacaatttta 2700 ttggatcaatttaactggtt gtatacacca aagcaacttc ctagtcaagt tctggtaaga 2760 attagacatgctcaaaaacc agaaattgca aagttgaaat tattatcaga taataaactg 2820 gaaataacatttaaaaatcc tgttataagt gttgcatctg gacagtttgg tgtattatat 2880 acacttgatcaaatttgttt aggagcagga ttaatttaag gtgatattat tttctttgat 2940 ggttgtgaatttgtaattaa tgactaattt aattaaatat ttaaaagaac tccaaaactg 3000 gctgtttgattatgtaaaaa aatctaaagc taaaggtgtt atttttggct tatctggagg 3060 aattgattcagcagttgttg ctgctattgc taaagaaact tttggttttg aaaaccattt 3120 agctttaataatgcatatta ataattcaaa acttgatttt caagcaacta gtgaacttgt 3180 taaaaaaatgcaatttaata gtattaacat tgaactggaa gagagtttca atctgttagt 3240 aaaaacccttggaatagatc caaaaaaaga ttttttaaca gctggtaaca ttaaagcacg 3300 tttacggatgataactttat atgcttatgc tcaaaaacac aacttcttag ttttaggtac 3360 tggtaattttgtagagtata cacttggtta tttcacaaaa tgaggagatg gagcttgtga 3420 tattgctcctttagcatggc ttttaaaaga ggacgtttac aaattagcta agcattttaa 3480 tattcctgaaattgtaatca caagagcgcc aactgctagt ctttttgaag ggcaaactga 3540 tgagacagagatgggcatta cttataagga acttgatcaa tatttaaaag gtgatttaat 3600 acttagttcagaaaagcaaa aaattgtttt agatttgaaa gcaaaagcag agcataaaca 3660 taattcacctttgaaattta aacatctcta taatttccag aactaa 3706 19 232 DNA E. coli 19gatctattta tttagagatc tgttctattg tgatctctta ttaggatcgc actgccctgt 60ggataacaag gatccggctt ttaagatcaa caacctggaa aggatcatta actgtgaatg 120atcggtgatc ctggaccgta taagctggga tcagaatgag gggttataca caactcaaaa 180actgaacaac agttgttctt tggataacta ccggttgatc caagcttcct ga 232

What is claimed is:
 1. A basic genetic operating system for anautonomous prototrophic nanomachine comprising a nanomachine genomeencoding a minimal gene set sufficient for viability.
 2. The basicgenetic operating system of claim 1, wherein said minimal gene setfurther comprises the functional categories of transcription,translation, aerobic metabolism, glycolysis/pyruvatedehydrogenase/pentose phosphate pathways, carbohydrate metabolism,central intermediary metabolism, nucleotide metabolism, transport andbinding proteins, and housekeeping functions.
 3. The basic geneticoperating system of claim 2, wherein said nanomachine genome directssynthesis of said functional categories in a relative order comprisingtranscription, translation, aerobic metabolism and glycolysis/pyruvatedehydrogenase/pentose phosphate pathways.
 4. The basic genetic operatingsystem of claim 3, wherein said relative order further comprises arelative temporal order.
 5. The basic genetic operating system of claim3, wherein said relative order further comprises a relative physicalorder.
 6. The basic genetic operating system of claim 1, furthercomprising a minimal gene set being devoid of at least one gene selectedfrom the group consisting of MG008, MG009, MG056, MG221, MG332, MG448 orMG449, an ortholog or a nonorthologous gene displacement thereof.
 7. Thebasic genetic operating system of claim 1, wherein said nanomachinegenome further comprises less than about 140 kilobases (kb) in size. 8.The basic genetic operating system of claim 1, wherein said minimal geneset sufficient for viability further comprises about 152 or lessfundamental genes.
 9. The basic genetic operating system of claim 8,wherein said fundamental genes further comprise about 14 genes in atranscription gene category, about 90 genes in a translation genecategory, about 13 genes in an aerobic metabolism gene category, about16 genes in a glycolysis/pyruvate dehydrogenase/pentose phosphatepathways gene category, about 3 genes in a carbohydrate metabolism genecategory, about 3 genes in a central intermediary metabolism genecategory, about 2 genes in a nucleotide metabolism gene category, about10 genes in a transport/binding protein gene category and about 1 genesin a housekeeping function gene category.
 10. The basic geneticoperating system of claim further comprise substantially the samefundamental genes show in FIG. 1, orthologs or nonothorologousdisplacements thereof.
 11. The basic genetic operation system of claim1, further comprising one or more genes selected from a replication genecategory.
 12. The basic genetic operation system of claim 1, furthercomprising one or more genes selected from the group consisting of atranslation gene category, a central intermediary metabolism category, anucleotide metabolism gene category, a phosphotransferase system (PTS)gene category, a signal transduction regulation gene category, atransport/binding protein gene category, a particle division genecategory, a chaperone system gene category, a fatty acid/lipidmetabolism gene category, a particle envelope gene category and ahousekeeping function gene category.
 13. The basic genetic operatingsystem of claim 1, further comprising an expression control region forthe production of a biomolecule.
 14. The basic genetic operating systemof claim 13, wherein said biomolecule further comprises an RNA.
 15. Thebasic genetic operating system of claim 13, wherein said biomoleculefurther comprises a polypeptide.
 16. An autonomous prototrophicnanomachine autonomous prototrophic viability and a particle envelope.17. The autonomous prototrophic nanomachine of claim 16, wherein saidparticle envelope further comprises a membrane.
 18. The autonomousprototrophich nanomachine of claim 16, wherein said particle envelopefurther comprises a biocompatible material.
 19. The autonomousprototrophic nanomachine of claim 16, wherein said basic geneticoperating system further comprises an expression control region for theproduction of a biomolecule.
 20. The autonomous prototrophic nanomachineof claim 19, wherein said biomolecule further comprises an RNA.
 21. Theautonomous prototrophic nanomacnine of claim 19, wherein saidbiomolecule further comprises a polypeptide.
 22. A basic geneticoperating system for an autonomous auxotrophic nanomachine comprising ananomachine genome encoding a minimal gene set sufficient for viabilityin the presence of an auxotrophic biomolecule.
 23. The basic geneticoperating system of claim 22, wherein said minimal gene set furthercomprises the functional categories of transcription, translation,aerobic metabolism, glycolysis/pyruvate dehydrogenase/pentose phosphatepathways, carbohydrate metabolism, central intermediary metabolism,nucleotide metabolism, transport and binding proteins, and housekeepingfunctions.
 24. The basic genetic operating system of claim 23, whereinsaid nanomachine genome directs synthesis of said functional categoriesin a relative order comprising transcription, translation, aerobicmetabolism and glycolysis/pyruvate dehydrogenase/pentose phosphatepathways.
 25. The basic genetic operating system of claim 24, whereinsaid relative order further comprises a relative temporal order.
 26. Thebasic genetic operating system of claim 24, wherein said relative orderfurther comprises a relative physical order.
 27. The basic geneticoperating system of claim 22, further comprising a minimal gene setbeing devoid of at least one gene selected from the group consisting ofMG008, MG009, MG056, MG221, MG332, MG448 or MG449, an ortholog or anonorthologous gene displacement thereof.
 28. The basic geneticoperating system of claim 22, wherein said nanomachine genome furthercomprises less than about 140 kilobases (kb) in size.
 29. The basicgenetic operating system of claim viability further comprises about 151or less fundamental genes.
 30. The basic genetic operating system ofclaim 29, wherein said fundamental genes further comprise at least onenonfunctional gene selected from a minimal gene set of fundamental genesconsisting of about 14 genes in a transcription gene category, about 90genes in a translation gene category, about 13 genes in an aerobicmetabolism gene category, about 16 genes in a glycolysis/pyruvatedehydrogenase/pentose phosphate pathways gene category, about 3 genes ina carbohydrate metabolism gene category, about 3 genes in a centralintermediary metabolism gene category, about 2 genes in a nucleotidemetabolism gene category, about 10 genes in a transport/binding proteingene category and about 1 genes in a housekeeping function genecategory.
 31. The basic genetic operating system of claim 29, whereinsaid about 151 or less fundamental genes further comprise substantiallythe same fundamental genes show in FIG. 1, orthologs or nonothorologousdisplacements thereof.
 32. The basic genetic operation system of claim22, further comprising one or more genes selected from a replicationgene category.
 33. The basic genetic operation system of claim 22,further comprising one or more genes selected from the group consistingof a translation gene category, a central intermediary metabolismcategory, a nucleotide metabolism gene category, a phosphotransferasesystem (PTS) gene category, a signal transduction regulation genecategory, a transport/binding protein gene category, a particle divisiongene category, a chaperone system gene category, a fatty acid/lipidmetabolism gene category, a particle envelope gene category and ahousekeeping function gene category.
 34. The basic genetic operatingsystem of claim 22, further comprising an expression control region forthe production of a biomolecule.
 35. The basic genetic operating systemof claim 34, wherein said biomolecule further comprises an RNA.
 36. Thebasic genetic operating system of claim 34, wherein said biomoleculefurther comprises a polypeptide.
 37. An autonomous auxotrophicnanomachine comprising a basic genetic operating system for autonomousauxotrophic viability in the presence of an auxotrophic biomolecule anda particle envelope.
 38. The autonomous auxotrophic nanomachine of claim37, wherein said particle envelope further comprises a membrane.
 39. Theautonomous auxotrophich nanomachine of claim 37, wherein said particleenvelope further comprises a biocompatible material.
 40. The autonomousauxotrophic nanomachine of claim 37, wherein said basic geneticoperating system further comprises an expression control region for theproduction of a biomolecule.
 41. The autonomous auxotrophic nanomachineof claim 40, wherein said biomolecule further comprises an RNA.
 42. Theautonomous auxotrophic nanomacnine of claim 40, wherein said biomoleculefurther comprises a polypeptide.
 43. A basic genetic operating systemfor an autonomous prototrophic nanomachine comprising a nanomachinegenome encoding a minimal gene set sufficient for autonomousprototrophic replication, said nanomachine genome directing synthesis ofsaid minimal gene set in a relative order of functional categoriescomprising replication, transcription, translation, aerobic metabolismand glycolysis/pyruvate dehydrogenase/pentose phosphate pathways. 44.The basic genetic operating system of claim 43, wherein said functionalcategories of said minimal gene set further comprise carbohydratemetabolism, central intermediary metabolism, nucleotide metabolism,signal transduction regulation, transport and binding proteins, particledivision, chaperone system, fatty acid/lipid metabolism, particleenvelope and housekeeping functions.
 45. The basic genetic operatingsystem of claim 43, wherein said relative order further comprises arelative temporal order.
 46. The basic genetic operating system of claim43, wherein said relative order further comprises a relative physicalorder.
 47. The basic genetic operating system of claim 46, wherein saidrelative physical order further comprises relative to an origin ofreplication.
 48. The basic genetic operating system of claim 43, furthercomprising a bidirectional order.
 49. The basic genetic operating systemof claim 43, further comprising an expression control region for theproduction of a biomolecule.
 50. A basic genetic operating system for anautonomous protrophic nanomachine comprising a nanomachine genomeencoding a minimal gene set sufficient for directing autonomousprototrophic replication, said minimal gene set being devoid of at leastone gene selected from the group consisting of MG008, MG009, MG056,MG221, MG262, MG332, MG448 or MG449, an ortholog or a nonorthologousgene displacement thereof.
 51. The basic genetic operating system ofclaim 50, wherein said minimal gene set further comprises the functionalcategories of replication, transcription, translation, aerobicmetabolism, glycolysis/pyruvate dehydrogenase/pentose phosphatepathways, carbohydrate metabolism, central intermediary metabolism,nucleotide metabolism, signal transduction regulation, transport andbinding proteins, particle division, chaperone system, fatty acid/lipidmetabolism, particle envelope and housekeeping functions.
 52. The basicgenetic operating system of claim 50, further comprising one or moregenes selected from the group consisting of MG020, MG022, MG034, MG039,MG041, MG046, MG051, MG061, MG062, MG108, MG121, MG129, MG183, MG188,MG368, MG429 an ortholog or a nonorthologous gene displacement thereof.53. The basic genetic operating system of claim 50, further comprisingan expression control region for the production of a biomolecule.
 54. Abasic genetic operating system for an autonomous prototropic nanomachinecomprising a nanomachine genome encoding a minimal gene set sufficientfor directing autonomous prototrophic replication, said nanomachinegenome being less than about 250 kilobases (kb) in size.
 55. The basicgenetic operating system of claim 54, wherein said minimal gene setfurther comprises functional categories selected from the groupconsisting of replication, transcription, translation, aerobicmetabolism, glycolysis/pyruvate dehydrogenase/pentose phosphatepathways, carbohydrate metabolism, central intermediary metabolism,nucleotide metabolism, signal transduction regulation, transport andbinding proteins, particle division, chaperone system, fatty acid/lipidmetabolism, particle envelope and housekeeping functions.
 56. The basicgenetic operating system of claim 54 further comprising about 247 orless fundamental genes.
 57. The basic genetic operating system of claim56, wherein said fundamental genes further comprise about 24 genes in areplication gene category, about 14 genes in a transcription genecategory, about 94 genes in a translation gene category, about 13 genesin an aerobic metabolism gene category, about 16 genes in aglycolysis/pyruvate dehydrogenase/pentose phosphate pathways genecategory, about 3 genes in a carbohydrate metabolism gene category,about 13 genes in a central intermediary metabolism gene category, about18 genes in a nucleotide metabolism gene category, about 4 genes in asignal transduction regulation gene category, about 23 genes in atransport/binding protein gene category, about 4 genes in a particledivision gene category, about 11 genes in a chaperone system genecategory, about 3 genes in a fatty acid/lipid metabolism gene category,about 3 genes in a particle envelope gene category, and about 4 genes ina housekeeping function gene category.
 58. The basic genetic operatingsystem of claim 56, wherein said about 247 or less fundamental genesfurther comprise substantially the same fundamental genes show in FIG.2, orthologs or nonothorologous displacements thereof.
 59. The basicgenetic operating system of claim 57, further comprising one or moregenes selected from the group consisting of a translation gene category,a transcription gene category, a nucleotide metabolism gene category, aphosphotransferase system (PTS) gene category, and a fatty acid/lipidmetabolism gene category.
 60. The basic genetic operating system ofclaim 59, further comprising one or more genes selected from the groupconsisting of MG020, MG022, MG034, MG039, MG041, MG046, MG051, MG061,MG062, MG108, MG121, MG129, MG183, MG188, MG368, MG429, an ortholog or anonorthologous gene displacement thereof.
 61. The basic geneticoperating system of claim 54, further comprising an expression controlregion for the production of a biomolecule.
 62. A basic geneticoperating system for an autonomous prototrophic nanomachine comprising ananomachine genome encoding a minimal gene set sufficient for autonomousprototrophic replication of about 247 or less fundamental genes.
 63. Thebasic genetic operating system of claim 62 wherein said fundamentalgenes further comprise about 24 genes in a replication gene category,about 14 genes in a transcription gene category, about 94 genes in atranslation gene category, about 13 genes in an aerobic metabolism genecategory, about 16 genes in a glycolysis/pyruvate dehydrogenase/pentosephosphate pathways gene category, about 3 genes in a carbohydratemetabolism gene category, about 13 genes in a central intermediarymetabolism gene category, about 18 genes in a nucleotide metabolism genecategory, about 4 genes in a signal transduction regulation genecategory, about 23 genes in a transport/binding protein gene category,about 4 genes in a particle division gene category, about 11 genes in achaperone system gene category, about 3 genes in a fatty acid/lipidmetabolism gene category, about 3 genes in a particle envelope genecategory, and about 4 genes in a housekeeping function gene category.64. The basic genetic operating system of claim 62, wherein said about247 or less fundamental genes further comprise substantially the samefundamental genes show in FIG. 2, orthologs or nonothorologousdisplacements thereof.
 65. The basic genetic operating system of claim62, further comprising one or more genes selected from the groupconsisting of a translation gene category, a transcription genecategory, a nucleotide metabolism gene category, a phosphotransferasesystem (PTS) gene category, and a fatty acid/lipid metabolism genecategory.
 66. The basic genetic operating system of claim 63, furthercomprising one or more genes selected from the group consisting ofMG020, MG022, MG034, MG039, MG041, MG046, MG051, MG061, MG062, MG108,MG121, MG129, MG183, MG188, MG368, MG429, ortholog or nonorthologousgene displacement thereof.
 67. The basic genetic operating system ofclaim 62, further comprising an expression control region for theproduction of a biomolecule.
 68. An autonomous prototrophic nanomachinecomprising a basic genetic operating system for autonomous prototrophicreplication and a particle envelope.
 69. The autonomous prototrophicnanomachine of claim 68, wherein said particle envelope furthercomprises a membrane.
 70. The autonomous prototrophic nanomachine ofclaim 68, wherein said particle envelope further comprises abiocompatible material.
 71. The autonomous prototrophic nanomachine ofclaim 68, wherein said basic genetic operating system further comprisesan expression control region for the production of a biomolecule. 72.The autonomous prototrophic nanomachine of claim 71, wherein saidbiomolecule further comprises an RNA.
 73. The autonomous prototrophicnanomacnine of claim 71, wherein said biomolecule further comprises apolypeptide.
 74. A basic genetic operating system for an autonomousauxotrophic nanomachine comprising a nanomachine genome encoding aminimal gene set sufficient for autonomous replication in the presenceof an auxotrophic biological molecule, said nanomachine genome directingsynthesis of said minimal gene set in a relative order of functionalcategories comprising replication, transcription, translation, aerobicmetabolism and glycolysis/pyruvate dehydrogenase/pentose phosphatepathways.
 75. The basic genetic operating system of claim 74, whereinsaid other functional categories of said minimal gene set furthercomprise carbohydrate metabolism, central intermediary metabolism,nucleotide metabolism, signal transduction regulation, transport andbinding proteins, particle division, chaperone system, fatty acid/lipidmetabolism, particle envelope and housekeeping functions.
 76. The basicgenetic operating system of claim 74, wherein said relative orderfurther comprises a relative temporal order.
 77. The basic geneticoperating system of claim 74, wherein said relative order furthercomprises a relative physical order.
 78. The basic genetic operatingsystem of claim 77, wherein said relative physical order furthercomprises relative to an origin of replication.
 79. The basic geneticoperating system of claim 74, further comprising a bidirectional order.80. The basic genetic operating system of claim 74, further comprisingan expression control region for the production of a biomolecule.
 81. Abasic genetic operating system for an autonomous auxotrophic nanomachinecomprising a nanomachine genome encoding a minimal gene set sufficientfor directing autonomous replication in the presence of an auxotrophicbiological molecule, said minimal gene set being devoid of at least onegene selected from the group consisting of MG008, MG009, MG056, MG221,MG262, MG332, MG448 or MG449, an ortholog or a nonorthologous genedisplacement thereof.
 82. The basic genetic operating system of claim81, wherein said minimal gene set further comprises the functionalcategories of replication, transcription, translation, aerobicmetabolism, glycolysis/pyruvate dehydrogenase/pentose phosphatepathways, carbohydrate metabolism, central intermediary metabolism,nucleotide metabolism, signal transduction regulation, transport andbinding proteins, particle division, chaperone system, fatty acid/lipidmetabolism, particle envelope and housekeeping functions.
 83. The basicgenetic operating system of claim 81, further comprising one or moregenes selected from the group consisting of MG020, MG022, MG034, MG039,MG041, MG046, MG051, MG061, MG062, MG108, MG121, MG129, MG183, MG188,MG368, MG429, an ortholog or a nonorthologous gene displacement thereof.84. The basic genetic operating system of claim 81, further comprisingan expression control region for the production of a biomolecule.
 85. Abasic genetic operating system for an autonomous auxotrophic nanomachinecomprising a nanomachine genome encoding a minimal gene set sufficientfor directing autonomous auxotrophic replication in the presence of anauxotrophic biological molecule, said nanomachine genome being less thanabout 250 kilobases (kb) in size.
 86. The basic genetic operating systemof claim 85, wherein said minimal gene set further comprises functionalcategories selected from the group consisting of replication,transcription, translation, aerobic metabolism, glycolysis/pyruvatedehydrogenase/pentose phosphate pathways, carbohydrate metabolism,central intermediary metabolism, nucleotide metabolism, signaltransduction regulation, transport and binding proteins, particledivision, chaperone system, fatty acid/lipid metabolism, particleenvelope and housekeeping functions.
 87. The basic genetic operatingsystem of claim 85, further comprising about 246 or less fundamentalgenes.
 88. The basic genetic operating system of claim 87, wherein saidfundamental genes further comprise at least one nonfunctional geneselected from a minimal gene set of fundamental genes consisting ofabout 24 genes in a replication gene category, about 14 genes in atranscription gene category, about 94 genes in a translation genecategory, about 13 genes in an aerobic metabolism gene category, about16 genes in a glycolysis/pyruvate dehydrogenase/pentose phosphatepathways gene category, about 3 genes in a carbohydrate metabolism genecategory, about 13 genes in a central intermediary metabolism genecategory, about 18 genes in a nucleotide metabolism gene category, about4 genes in a signal transduction regulation gene category, about 23genes in a transport/binding protein gene category, about 4 genes in aparticle division gene category, about 11 genes in a chaperone systemgene category, about 3 genes in a fatty acid/lipid metabolism genecategory, about 3 genes in a particle envelope gene category, and about4 genes in a housekeeping function gene category.
 89. The basic geneticoperating system of claim 87, wherein said about 246 or less fundamentalgenes further comprise substantially the same fundamental genes show inFIG. 2, orthologs or nonothorologous displacements thereof.
 90. Thebasic genetic operating system of claim 88, further comprising one ormore genes selected from the group consisting of a translation genecategory, a transcription gene category, a nucleotide metabolism genecategory, a phosphotransferase system (PTS) gene category, and a fattyacid/lipid metabolism gene category.
 91. The basic genetic operatingsystem of claim 90, further comprising one or more genes selected fromthe group consisting of MG020, MG022, MG034, MG039, MG041, MG046, MG051,MG061, MG062, MG108, MG121, MG129, MG183, MG188, MG368, MG429, anortholog or a nonorthologous gene displacement thereof.
 92. The basicgenetic operating system of claim 85, further comprising an expressioncontrol region for the production of a biomolecule.
 93. A basic geneticoperating system for an autonomous auxotrophic nanomachine comprising ananomachine genome encoding a minimal gene set sufficient for autonomousreplication in the presence of an auxotrophic biological molecule ofabout 246 or less fundamental genes.
 94. The basic genetic operatingsystem of claim 93, wherein said fundamental genes further compriseabout 24 genes in a replication gene category, about 14 genes in atranscription gene category, about 94 genes in a translation genecategory, about 13 genes in an aerobic metabolism gene category, about16 genes in a glycolysis/pyruvate dehydrogenase/pentose phosphatepathways gene category, about 3 genes in a carbohydrate metabolism genecategory, about 13 genes in a central intermediary metabolism genecategory, about 18 genes in a nucleotide metabolism gene category, about4 genes in a signal transduction regulation gene category, about 23genes in a transport/binding protein gene category, about 4 genes in aparticle division gene category, about 11 genes in a chaperone systemgene category, about 3 genes in a fatty acid/lipid metabolism genecategory, about 3 genes in a particle envelope gene category, and about4 genes in a housekeeping function gene category.
 95. The basic geneticoperating system of claim 93, wherein said about 246 or less fundamentalgenes further comprise substantially the same fundamental genes show inFIG. 2, orthologs or nonothorologous displacements thereof.
 96. Thebasic genetic operating system of claim 93, further comprising one ormore genes selected from the group consisting of a translation genecategory, a transcription gene category, a nucleotide metabolism genecategory, a phosphotransferase system (PTS) gene category, and a fattyacid/lipid metabolism gene category.
 97. The basic genetic operatingsystem of claim 94, further comprising one or more genes selected fromthe group consisting of MG020, MG022, MG034, MG039, MG041, MG046, MG051,MG061, MG062, MG108, MG121, MG129, MG183, MG188, MG368, MG429, orthologor nonorthologous gene displacement thereof.
 98. The basic geneticoperating system of claim 93, further comprising an expression controlregion for the production of a biomolecule.
 99. An autonomousauxotrophic nanomachine comprising a basic genetic operating system forautonomous replication in the presence of an auxotrophic biologicalmolecule and a particle envelope.
 100. The autonomous auxotrophicnanomachine of claim 99, wherein said particle envelope furthercomprises a membrane.
 101. The autonomous auxotrophic nanomachine ofclaim 99, wherein said particle envelope further comprises abiocompatible material.
 102. The autonomous auxotrophic nanomachine ofclaim 99, wherein said basic genetic operating system further comprisesan expression control region for the production of a biomolecule. 103.The autonomous auxotrophic nanomachine of claim 102, wherein saidbiomolecule further comprises an RNA.
 104. The autonomous auxotrophicnanomacnine of claim 102, wherein said biomolecule further comprises apolypeptide.